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Matsuda Tadashi
| Faculty of Pharmaceutical Sciences Molecular Pharmaceutical Sciences Regulation for Immune Signaling | Specially Appointed Professor |
Researcher basic information
■ Degree■ URL
researchmap URLホームページURL■ Various IDs
J-Global ID■ Research Keywords and Fields
Research KeywordResearch Field
- Life Science, Immunology
- Life Science, Pharmacology
- Life Science, Pharmaceutical hygiene and biochemistry
- Bachelor's degree program, School of Pharmaceutical Sciences and Pharmacy
- Master's degree program, Graduate School of Life Science
- Doctoral (PhD) degree program, Graduate School of Life Science
Research activity information
■ Awards- Sep. 2021, 秋山記念生命科学振興財団, 秋山財団賞
松田 正 - Sep. 2021, 伊藤医薬学術交流財団, 伊藤太郎学術賞
松田 正 - 2000, ISI引用最高栄誉賞
- 2000, ISI Citation Laureate Award
- A selective RPL15 PROTAC degrader enhances anti-PD-1 immunotherapy in a murine melanoma tumor model.
Runa Takahashi; Kazuki Yamamoto; Hikaru Toya; Haruka Shoji; Kohei Kawanishi; Kyoka Momosaki; Miyuki Yabe; Ken Takashima; Ryuta Muromoto; Satoshi Ichikawa; Tadashi Matsuda; Yuichi Kitai
Oncogene, 44, 50, 4846, 4854, Dec. 2025, [International Magazine]
English, Scientific journal, Damage-associated molecular patterns (DAMPs) are secreted from damaged or dying cells and activate innate immune signaling via pattern-recognition receptors such as Toll-like receptors and cGAS. We previously showed that topotecan, a chemotherapeutic drug and topoisomerase I (TOP1) inhibitor, binds to ribosomal protein RPL15 and induces the secretion of DAMPs from cancer cells, which activate cGAS-STING signaling in dendritic cells. RPL15-knockdown B16-F10 melanoma tumors were sensitized to anti-PD-1 antibody, suggesting that RPL15 inhibition may have the potential to improve immune checkpoint inhibitor efficacy. However, topotecan and its derivatives, including SN-38, are highly cytotoxic because of their TOP1 inhibitory activity. Here, we synthesized SN-38-conjugated pomalidomide (SN38-PROTAC) and showed that SN38-PROTAC induced ubiquitin-mediated degradation of RPL15, but not TOP1. SN38-PROTAC treatment induced DAMP secretion from cancer cells, which activated cGAS-STING signaling in dendritic cells. The cytotoxicity of SN38-PROTAC in MCF7 cells was 100-fold lower than SN-38. SN38-PROTAC treatment increased the CTL/Treg ratio in tumors and sensitized B16-F10 tumors to anti-PD-1 antibody in a mouse model. The enhanced antitumor effects of SN38-PROTAC and anti-PD-1 antibody combination were abolished in STING-deficient mice. Our results indicate that SN38-PROTAC, which induces RPL15 degradation, has the potential to enhance ICI efficacy in PD-1-resistant cancer with low cytotoxicity. - Nogo-A-cleaved amino-terminal fragment but not Nogo-B regulates STAT3 activation
Yuichi Sekine; Amane Hatasa; Tadashi Matsuda; Masahiro Fujimuro
Biochemical and Biophysical Research Communications, 153205, 153205, Elsevier BV, Dec. 2025
Scientific journal - Ozonated olive oil inhibits melanoma proliferation by inducing ferroptosis
Seong-Jin An; Jun-Ichi Kashiwakura; Akira Katsuyama; Sumihito Togi; Yuichi Kitai; Ryuta Muromoto; Toshiaki Miura; Satoshi Ichikawa; Tadashi Matsuda
Biochemistry and Biophysics Reports, 44, 102267, 102267, Elsevier BV, Dec. 2025
Scientific journal - STAP-1-derived peptide suppresses TCR-mediated T cell activation and ameliorates immune diseases by inhibiting STAP-1-LCK binding.
Yuto Sasaki; Kota Kagohashi; Shoya Kawahara; Yuichi Kitai; Ryuta Muromoto; Kenji Oritani; Jun-Ichi Kashiwakura; Tadashi Matsuda
ImmunoHorizons, 9, 6, 26 Apr. 2025, [International Magazine]
English, Scientific journal, Signal-transducing adaptor protein-1 (STAP-1) is an adaptor protein specifically expressed in immune cells, such as T cells. We previously demonstrated that STAP-1 positively upregulates T cell receptor (TCR)-mediated T cell activation by interacting with LCK and phospholipase C-γ1 and affecting autoimmune demyelination and airway inflammation. In this study, we aimed to generate a new STAP-1-derived peptide, iSP1, to inhibit the STAP-1-LCK interaction. We also analyzed its function in vitro and in vivo. iSP1 successfully interfered with STAP-1-LCK binding and suppressed TCR-mediated signal transduction, interleukin-2 production, and human and murine T cell proliferation. Additionally, iSP1 prevented the progression of experimental autoimmune encephalomyelitis by inhibiting Th1 and Th17 cell infiltration. Our findings suggest iSP1 as a new therapeutic immunomodulatory agent for T cell-mediated autoimmune diseases. - STAP-2 facilitates insulin signaling through binding to CAP/c-Cbl and regulates adipocyte differentiation
Yuichi Sekine; Kazuna Kikkawa; Sachie Honda; Yuto Sasaki; Shoya Kawahara; Akihiro Mizushima; Sumihito Togi; Masahiro Fujimuro; Kenji Oritani; Tadashi Matsuda
Scientific Reports, 14, 1, 09 Mar. 2024
English, Scientific journal - Tyrosinase regulates the motility of human melanoma cell line A375 through its hydroxylase enzymatic activity
Sachie Honda; Tadashi Matsuda; Masahiro Fujimuro; Yuichi Sekine
Biochemical and Biophysical Research Communications, 707, 149785, 149785, Mar. 2024
English, Scientific journal - Role of Signal-Transducing Adaptor Protein-1 for T Cell Activation and Pathogenesis of Autoimmune Demyelination and Airway Inflammation
Kota Kagohashi; Yuto Sasaki; Kiyotaka Ozawa; Takuya Tsuchiya; Shoya Kawahara; Kodai Saitoh; Michiko Ichii; Jun Toda; Yasuyo Harada; Masato Kubo; Yuichi Kitai; Ryuta Muromoto; Kenji Oritani; Jun-ichi Kashiwakura; Tadashi Matsuda
The Journal of Immunology, 212, 6, 05 Feb. 2024
English, Scientific journal - Potential of targeting signal-transducing adaptor protein-2 in cancer therapeutic applications.
Taiga Maemoto; Yuto Sasaki; Fumiya Okuyama; Yuichi Kitai; Kenji Oritani; Tadashi Matsuda
Exploration of targeted anti-tumor therapy, 5, 2, 251, 259, 2024, [International Magazine]
English, Scientific journal, Adaptor proteins play essential roles in various intracellular signaling pathways. Signal-transducing adaptor protein-2 (STAP-2) is an adaptor protein that possesses pleckstrin homology (PH) and Src homology 2 (SH2) domains, as well as a YXXQ signal transducer and activator of transcription 3 (STAT3)-binding motif in its C-terminal region. STAP-2 is also a substrate of breast tumor kinase (BRK). STAP-2/BRK expression is deregulated in breast cancers and enhances STAT3-dependent cell proliferation. In prostate cancer cells, STAP-2 interacts with and stabilizes epidermal growth factor receptor (EGFR) after stimulation, resulting in the upregulation of EGFR signaling, which contributes to cancer-cell proliferation and tumor progression. Therefore, inhibition of the interaction between STAP-2 and BRK/EGFR may be a possible therapeutic strategy for these cancers. For this purpose, peptides that interfere with STAP-2/BRK/EGFR binding may have great potential. Indeed, the identified peptide inhibitor successfully suppressed the STAP-2/EGFR protein interaction, EGFR stabilization, and cancer-cell growth. Furthermore, the peptide inhibitor suppressed tumor formation in human prostate- and lung-cancer cell lines in a murine xenograft model. This review focuses on the inhibitory peptide as a promising candidate for the treatment of prostate and lung cancers. - The Atypical Dual Specificity Phosphatase DUSP15 Regulates Jak1-Mediated STAT3 Activation.
Kazuna Kikkawa; Tadashi Matsuda; Masahiro Fujimuro; Yuichi Sekine
Biological & pharmaceutical bulletin, 47, 9, 1487, 1493, 2024, [Domestic magazines]
English, Scientific journal - [Understanding New Regulatory Mechanism of TCR Signal Transduction].
Jun-Ichi Kashiwakura; Tadashi Matsuda
Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan, 144, 5, 497, 501, 2024, [Domestic magazines]
Japanese, Scientific journal - Potential therapeutic applications of targeting signal-transducing adaptor protein-2 in autoimmune diseases
Yuto Sasaki; Shoya Kawahara; Yuichi Sekine; Jun-Ichi Kashiwakura; Kenji Oritani; Tadashi Matsuda
Exploration of Immunology, 3, 6, 604, 612, Open Exploration Publishing, 28 Dec. 2023
Scientific journal, Adaptor proteins are involved in various immune responses via the modulation of many signaling pathways. Signal-transducing adaptor protein-2 (STAP-2) is an adaptor protein that contains typical domains such as the pleckstrin homology (PH) domain, Src homology domain, and a proline-rich region from the N-terminal region. In T cells, STAP-2 positively regulates T cell receptor (TCR)-mediated signaling by associating with CD3ζ immunoreceptor tyrosine-based activation motifs (ITAMs) and lymphocyte-specific protein tyrosine kinase (LCK). Therefore, a peptide that inhibits the interaction between STAP-2 and CD3ζ ITAMs is likely to suppress TCR-mediated T cell activation, as well as T cell-mediated diseases. As expected, the peptide successfully inhibited the STAP-2/CD3ζ ITAM interaction and suppressed TCR-mediated signaling, cell proliferation, and interleukin (IL)-2 production in human/murine T cells. Furthermore, this inhibitor suppressed the pathogenesis of experimental autoimmune encephalomyelitis (EAE), which is widely recognized as a mouse model of multiple sclerosis, via the downregulation of T cell activation and infiltration of T helper (Th) 1/Th17 cells. These results suggest a new strategy for the treatment of multiple sclerosis and other immune diseases. - STAP-2 negatively regulates BCR-mediated B cell activation by recruiting tyrosine-protein kinase CSK to LYN.
Jun-Ichi Kashiwakura; Shoya Kawahara; Iori Inagaki; Kyosuke Inui; Kodai Saitoh; Kota Kagohashi; Yuto Sasaki; Fuki Kobayashi; Yuichi Kitai; Ryuta Muromoto; Kenji Oritani; Tadashi Matsuda
FEBS letters, 597, 19, 2433, 2445, 05 Sep. 2023, [International Magazine]
English, Scientific journal - STAP-2–Derived Peptide Suppresses TCR-Mediated Signals to Initiate Immune Responses
Yuto Sasaki; Kodai Saitoh; Kota Kagohashi; Toyoyuki Ose; Shoya Kawahara; Yuichi Kitai; Ryuta Muromoto; Yuichi Sekine; Michiko Ichii; Akihiko Yoshimura; Kenji Oritani; Jun-ichi Kashiwakura; Tadashi Matsuda
The Journal of Immunology, 211, 5, 755, 766, 07 Jul. 2023
English, Scientific journal - The Physiological and Pathophysiological Role of IL-6/STAT3-Mediated Signal Transduction and STAT3 Binding Partners in Therapeutic Applications
Tadashi Matsuda
BIOLOGICAL & PHARMACEUTICAL BULLETIN, 46, 3, 364, 378, Mar. 2023
English - Signal-transducing adaptor protein-2 modulates T-cell functions
Tadashi Matsuda; Yuto Sasaki; Kota Kagohashi; Kodai Saitoh; Yuichi Sekine; Jun-Ichi Kashiwakura; Kenji Oritani
Exploration of Immunology, 771, 782, Open Exploration Publishing, 27 Dec. 2022
Scientific journal, Immune responses are orchestrated by controlling the initiation, magnitude, and duration of various signaling pathways. Adaptor proteins act as positive or negative regulators by targeting critical molecules of signaling cascades. Signal-transducing adaptor protein-2 (STAP-2) contains typical features of adaptor proteins, like a pleckstrin homology (PH) domain in the N-terminal region and a Src homology 2 (SH2) domain in the central region. STAP-2 binds to a variety of signaling or transcriptional molecules to control multiple steps of inflammatory/immune responses. STAP-2 enhances T-cell receptor (TCR)-mediated signaling via the association with TCR-proximal CD3ζ immunoreceptor tyrosine-based activation motifs (ITAMs) and lymphocyte-specific protein tyrosine kinase (Lck). STAP-2 decreases adherence of T-cells to fibronectin (FN) through an association with focal adhesion kinase (Fak) and Casitas B-lineage Lymphoma (c-Cbl), and increases chemotaxis of T-cells toward stromal cell-derived factor-1α (SDF-1α) through interactions with Vav1 and Ras-related C3 botulinum toxin substrate 1 (Rac1). STAP-2 positively regulates activation-induced cell deathrough the association with Fas and caspase-8. This review describes the current knowledge of the roles of STAP-2 in T-cell-dependent immune responses and the possible clinical utility of STAP-2-targeting therapies. - CARD11 mutation and HBZ expression induce lymphoproliferative disease and adult T-cell leukemia/lymphoma
Takuro Kameda; Kotaro Shide; Ayako Kamiunten; Yasunori Kogure; Daisuke Morishita; Junji Koya; Yuki Tahira; Keiichi Akizuki; Takako Yokomizo-Nakano; Sho Kubota; Kosuke Marutsuka; Masaaki Sekine; Tomonori Hidaka; Yoko Kubuki; Yuichi Kitai; Tadashi Matsuda; Akinori Yoda; Takayuki Ohshima; Midori Sugiyama; Goro Sashida; Keisuke Kataoka; Seishi Ogawa; Kazuya Shimoda
Communications Biology, 5, 1, Dec. 2022
Scientific journal - The Functional Properties and Physiological Roles of Signal-Transducing Adaptor Protein-2 in the Pathogenesis of Inflammatory and Immune Disorders.
Jun-Ichi Kashiwakura; Kenji Oritani; Tadashi Matsuda
Biomedicines, 10, 12, 30 Nov. 2022, [International Magazine]
English, Scientific journal, Adaptor molecules play a crucial role in signal transduction in immune cells. Several adaptor molecules, such as the linker for the activation of T cells (LAT) and SH2 domain-containing leukocyte protein of 76 kDa (SLP-76), are essential for T cell development and activation following T cell receptor (TCR) aggregation, suggesting that adaptor molecules are good therapeutic targets for T cell-mediated immune disorders, such as autoimmune diseases and allergies. Signal-transducing adaptor protein (STAP)-2 is a member of the STAP family of adaptor proteins. STAP-2 functions as a scaffold for various intracellular proteins, including BRK, signal transducer, and activator of transcription (STAT)3, STAT5, and myeloid differentiation primary response protein (MyD88). In T cells, STAP-2 is involved in stromal cell-derived factor (SDF)-1α-induced migration, integrin-dependent cell adhesion, and Fas-mediated apoptosis. We previously reported the critical function of STAP-2 in TCR-mediated T cell activation and T cell-mediated autoimmune diseases. Here, we review how STAP-2 affects the pathogenesis of T cell-mediated inflammation and immune diseases in order to develop novel STAP-2-targeting therapeutic strategies. - A peptide derived from adaptor protein STAP-2 inhibits tumor progression by downregulating epidermal growth factor receptor signaling.
Taiga Maemoto; Yuichi Kitai; Runa Takahashi; Haruka Shoji; Shunsuke Yamada; Shiho Takei; Daiki Ito; Ryuta Muromoto; Jun-Ichi Kashiwakura; Haruka Handa; Ari Hashimoto; Shigeru Hashimoto; Toyoyuki Ose; Kenji Oritani; Tadashi Matsuda
The Journal of biological chemistry, 299, 1, 102724, 102724, 18 Nov. 2022, [International Magazine]
English, Scientific journal - Central Roles of STAT3-Mediated Signals in Onset and Development of Cancers: Tumorigenesis and Immunosurveillance.
Shigeru Hashimoto; Ari Hashimoto; Ryuta Muromoto; Yuichi Kitai; Kenji Oritani; Tadashi Matsuda
Cells, 11, 16, 22 Aug. 2022, [International Magazine]
English, Scientific journal, Since the time of Rudolf Virchow in the 19th century, it has been well-known that cancer-associated inflammation contributes to tumor initiation and progression. However, it remains unclear whether a collapse of the balance between the antitumor immune response via the immunological surveillance system and protumor immunity due to cancer-related inflammation is responsible for cancer malignancy. The majority of inflammatory signals affect tumorigenesis by activating signal transducer and activation of transcription 3 (STAT3) and nuclear factor-κB. Persistent STAT3 activation in malignant cancer cells mediates extremely widespread functions, including cell growth, survival, angiogenesis, and invasion and contributes to an increase in inflammation-associated tumorigenesis. In addition, intracellular STAT3 activation in immune cells causes suppressive effects on antitumor immunity and leads to the differentiation and mobilization of immature myeloid-derived cells and tumor-associated macrophages. In many cancer types, STAT3 does not directly rely on its activation by oncogenic mutations but has important oncogenic and malignant transformation-associated functions in both cancer and stromal cells in the tumor microenvironment (TME). We have reported a series of studies aiming towards understanding the molecular mechanisms underlying the proliferation of various types of tumors involving signal-transducing adaptor protein-2 as an adaptor molecule that modulates STAT3 activity, and we recently found that AT-rich interactive domain-containing protein 5a functions as an mRNA stabilizer that orchestrates an immunosuppressive TME in malignant mesenchymal tumors. In this review, we summarize recent advances in our understanding of the functional role of STAT3 in tumor progression and introduce novel molecular mechanisms of cancer development and malignant transformation involving STAT3 activation that we have identified to date. Finally, we discuss potential therapeutic strategies for cancer that target the signaling pathway to augment STAT3 activity. - Identification of RPL15 60S Ribosomal Protein as a Novel Topotecan Target Protein That Correlates with DAMP Secretion and Antitumor Immune Activation.
Shunsuke Yamada; Yuichi Kitai; Takashi Tadokoro; Runa Takahashi; Haruka Shoji; Taiga Maemoto; Marie Ishiura; Ryuta Muromoto; Jun-Ichi Kashiwakura; Ken J Ishii; Katsumi Maenaka; Taro Kawai; Tadashi Matsuda
Journal of immunology (Baltimore, Md. : 1950), 209, 1, 171, 179, 20 Jun. 2022, [International Magazine]
English, Scientific journal, Damage-associated molecular patterns (DAMPs) contribute to antitumor immunity during cancer chemotherapy. We previously demonstrated that topotecan (TPT), a topoisomerase I inhibitor, induces DAMP secretion from cancer cells, which activates STING-mediated antitumor immune responses. However, how TPT induces DAMP secretion in cancer cells is yet to be elucidated. Here, we identified RPL15, a 60S ribosomal protein, as a novel TPT target and showed that TPT inhibited preribosomal subunit formation via its binding to RPL15, resulting in the induction of DAMP-mediated antitumor immune activation independent of TOP1. TPT inhibits RPL15-RPL4 interactions and decreases RPL4 stability, which is recovered by CDK12 activity. RPL15 knockdown induced DAMP secretion and increased the CTL population but decreased the regulatory T cell population in a B16-F10 murine melanoma model, which sensitized B16-F10 tumors against PD-1 blockade. Our study identified a novel TPT target protein and showed that ribosomal stress is a trigger of DAMP secretion, which contributes to antitumor immunotherapy. - STAP-2 Is a Novel Positive Regulator of TCR-Proximal Signals.
Kodai Saitoh; Jun-Ichi Kashiwakura; Kota Kagohashi; Yuto Sasaki; Shoya Kawahara; Yuichi Sekine; Yuichi Kitai; Ryuta Muromoto; Michiko Ichii; Hiroko Nakatsukasa; Akihiko Yoshimura; Kenji Oritani; Tadashi Matsuda
Journal of immunology (Baltimore, Md. : 1950), 209, 1, 57, 68, 20 Jun. 2022, [International Magazine]
English, Scientific journal, TCR ligation with an Ag presented on MHC molecules promotes T cell activation, leading to the selection, differentiation, and proliferation of T cells and cytokine production. These immunological events are optimally arranged to provide appropriate responses against a variety of pathogens. We here propose signal-transducing adaptor protein-2 (STAP-2) as a new positive regulator of TCR signaling. STAP-2-deficient T cells showed reduced, whereas STAP-2-overexpressing T cells showed enhanced, TCR-mediated signaling and downstream IL-2 production. For the mechanisms, STAP-2 associated with TCR-proximal CD3ζ immunoreceptor tyrosine activation motifs and phosphorylated LCK, resulting in enhancement of their binding after TCR stimulation. In parallel, STAP-2 expression is required for full activation of downstream TCR signaling. Importantly, STAP-2-deficient mice exhibited slight phenotypes of CD4+ T-cell-mediated inflammatory diseases, such as experimental autoimmune encephalomyelitis, whereas STAP-2-overexpressing transgenic mice showed severe phenotypes of these diseases. Together, STAP-2 is an adaptor protein to enhance TCR signaling; therefore, manipulating STAP-2 will have an ability to improve the treatment of patients with autoimmune diseases as well as the chimeric Ag receptor T cell therapy. - Regulation of NFKBIZ gene promoter activity by STAT3, C/EBPβ, and STAT1
Ryuta Muromoto; Ami Sato; Yuki Komori; Kota Nariya; Yuichi Kitai; Jun-ichi Kashiwakura; Tadashi Matsuda
Biochemical and Biophysical Research Communications, Elsevier BV, May 2022
Scientific journal - A novel intramolecular negative regulation of mouse Jak3 activity by tyrosine 820.
Yuichi Sekine; Kazuna Kikkawa; Bruce A Witthuhn; Jun-Ichi Kashiwakura; Ryuta Muromoto; Yuichi Kitai; Masahiro Fujimuro; Kenji Oritani; Tadashi Matsuda
International immunology, 22 Feb. 2022, [International Magazine]
English, Scientific journal, Jak3, a member of the Janus kinase family, is essential for the cytokine receptor common gamma (γ) chain-mediated signaling. During activation of Jak3, tyrosine residues are phosphorylated and potentially regulate its kinase activity. We identified a novel tyrosine phosphorylation site within mouse Jak3, Y820, which is conserved in human Jak3, Y824. IL-2-induced tyrosine phosphorylation of Jak3 Y824 in human T cell line HuT78 cells was detected by using a phosphospecific, pY824, antibody. Mutation of mouse Jak3 Y820 to alanine (Y820A) showed increased autophosphorylation of Jak3 and enhanced STAT5 tyrosine phosphorylation and transcriptional activation. Stably expressed Jak3 Y820A in F7 cells, an IL-2 responsive mouse pro-B cell line Ba/F3, exhibited enhanced IL-2-dependent cell growth. Mechanistic studies demonstrated that interaction between Jak3 and STAT5 increased in Jak3 Y820A compared to Jak3 WT. These data suggest that Jak3 Y820 plays a role in negative regulation of Jak3-mediated STAT5 signaling cascade upon IL-2-stimulation. We speculate that this occurs through an interaction promoted by the tyrosine phosphorylated Y820 or a conformational change by Y820 mutation with either the STAT directly or with the recruitment of molecules such as phosphatases via a SH2 interaction. Additional studies will focus on these interactions as Jak3 plays a crucial role in disease and health. - Current understanding of the role of tyrosine kinase 2 signaling in immune responses.
Ryuta Muromoto; Kenji Oritani; Tadashi Matsuda
World journal of biological chemistry, 13, 1, 1, 14, 27 Jan. 2022, [International Magazine]
English, Scientific journal, Immune system is a complex network that clears pathogens, toxic substrates, and cancer cells. Distinguishing self-antigens from non-self-antigens is critical for the immune cell-mediated response against foreign antigens. The innate immune system elicits an early-phase response to various stimuli, whereas the adaptive immune response is tailored to previously encountered antigens. During immune responses, B cells differentiate into antibody-secreting cells, while naïve T cells differentiate into functionally specific effector cells [T helper 1 (Th1), Th2, Th17, and regulatory T cells]. However, enhanced or prolonged immune responses can result in autoimmune disorders, which are characterized by lymphocyte-mediated immune responses against self-antigens. Signal transduction of cytokines, which regulate the inflammatory cascades, is dependent on the members of the Janus family of protein kinases. Tyrosine kinase 2 (Tyk2) is associated with receptor subunits of immune-related cytokines, such as type I interferon, interleukin (IL)-6, IL-10, IL-12, and IL-23. Clinical studies on the therapeutic effects and the underlying mechanisms of Tyk2 inhibitors in autoimmune or chronic inflammatory diseases are currently ongoing. This review summarizes the findings of studies examining the role of Tyk2 in immune and/or inflammatory responses using Tyk2-deficient cells and mice. - IL-17 signaling is regulated through intrinsic stability control of mRNA during inflammation
Ryuta Muromoto; Kenji Oritani; Tadashi Matsuda
AIMS ALLERGY AND IMMUNOLOGY, 6, 3, 188, 199, 2022
English - Signal-transducing adaptor protein-1 and protein-2 in hematopoiesis and diseases
Michiko Ichii; Kenji Oritani; Jun Toda; Naoki Hosen; Tadashi Matsuda; Yuzuru Kanakura
Experimental Hematology, 105, 10, 17, Elsevier BV, Jan. 2022
Scientific journal - Perturbation of IL-17A response by environmental chemicals
MUROMOTO Ryuta; MATSUDA Tadashi
Annual Meeting of the Japanese Society of Toxicology, 49.1, S39-3, The Japanese Society of Toxicology, 2022
Japanese, IL-17A is a cytokine produced by immune cells and acts on non-immune cells such as epithelial cells to stimulate the production of chemokines and antimicrobial peptides. This IL-17A-initiated activation of cells is important for amplifying inflammation and eliminating fungi and bacteria, while an uncontrolled increase in IL-17A action leads to disease, as shown in psoriasis, multiple sclerosis, rheumatoid arthritis patients, and their mouse models. In this study, we report that the IL-17A-induced response is affected by environmental chemicals. We have found IκB-ζ as an IL-17A-induced protein by gene expression analysis using epidermal keratinocytes, and that IκB-ζ plays a role in the expression of other IL-17A-induced genes. The mechanism of IκB-ζ induction by IL-17A was the mRNA stabilization, which is caused by the inactivation of Regnase-1, an mRNA degrading enzyme. The signaling leading to the inactivation of Regnase-1 was inhibited by dimethyl fumarate, a drug used for multiple sclerosis treatment. On the other hand, benzo[a]pyrene, a ligand for aryl hydrocarbon receptor, suppressed the function of Regnase-1 and increased the amount of IκB-ζ mRNA and IL-6 mRNA, which are degradation targets by Regnase-1. In summary, the IL-17A signaling pathway and mRNA stability control mechanisms are positively or negatively affected by various environmental chemicals. These mechanisms may be targets for chemical-induced changes in inflammatory and immune responses. - Possible Therapeutic Applications of Targeting STAP Proteins in Cancer
Tadashi Matsuda; Kenji Oritani
BIOLOGICAL & PHARMACEUTICAL BULLETIN, 44, 12, 1810, 1818, Dec. 2021
English - Signal-transducing adaptor protein-2 has a nonredundant role for IL-33-triggered mast cell activation.
Jun-Ichi Kashiwakura; Nao Koizumi; Kodai Saitoh; Kota Kagohashi; Yuto Sasaki; Fuki Kobayashi; Shoya Kawahara; Yukie Yamauchi; Yuichi Kitai; Ryuta Muromoto; Kenji Oritani; Tadashi Matsuda
Biochemical and biophysical research communications, 572, 80, 85, 01 Oct. 2021, [Peer-reviewed], [International Magazine]
English, Scientific journal, Signal-transducing adaptor protein (STAP)-2 is one of the STAP family adaptor proteins and ubiquitously expressed in a variety types of cells. Although STAP-2 is required for modification of FcεRI signal transduction in mast cells, other involvement of STAP-2 in mast cell functions is unknown, yet. In the present study, we mainly investigated functional roles of STAP-2 in IL-33-induced mast cell activation. In STAP-2-deficient, but not STAP-1-deficient, mast cells, IL-33-induced IL-6 and TNF-α production was significantly decreased compared with that of wild-type mast cells. In addition, STAP-2-deficiency greatly reduced TLR4-mediated mast cell activation and cytokine production. For the mechanisms, STAP-2 directly binds to IKKα after IL-33 stimulation, leading to elevated NF-κB activity. In conclusion, STAP-2, but not STAP-1, participates in IL-33-induced mast cells activation. - STAP-2 adaptor protein regulates multiple steps of immune and inflammatory responses
Matsuda, T; K.Oritani
Biol. Pharm. Bull., 44, 7, 895, 901, Jul. 2021, [Peer-reviewed]
Scientific journal - Propolis suppresses cytokine production in activated basophils and basophil-mediated skin and intestinal allergic inflammation in mice.
Jun-Ichi Kashiwakura; Mari Yoshihara; Kodai Saitoh; Kota Kagohashi; Yuto Sasaki; Fuki Kobayashi; Iori Inagaki; Yuichi Kitai; Ryuta Muromoto; Tadashi Matsuda
Allergology international : official journal of the Japanese Society of Allergology, 70, 3, 360, 367, Jul. 2021, [Peer-reviewed], [International Magazine]
English, Scientific journal, BACKGROUND: Propolis is a resinous mixture produced by honey bees that contains cinnamic acid derivatives and flavonoids. Although propolis has been reported to inhibit mast cell functions and mast cell-dependent allergic responses, the effect of propolis on basophil biology remains unknown. This study aimed to investigate the inhibitory effect of propolis on FcεRI-mediated basophil activation. METHODS: To determine the inhibitory effect of propolis on basophil activation in vitro, cytokine production and FcεRI signal transduction were analyzed by ELISA and western blotting, respectively. To investigate the inhibitory effect of propolis in vivo, IgE-CAI and a food allergy mouse model were employed. RESULTS: Propolis treatment resulted in the suppression of IgE/antigen-induced production of IL-4, IL-6 and IL-13 in basophils. Phosphorylation of FcεRI signaling molecules Lyn, Akt and ERK was inhibited in basophils treated with propolis. While propolis did not affect the basophil population in the treated mice, propolis did inhibit IgE-CAI. Finally, ovalbumin-induced intestinal anaphylaxis, which involves basophils and basophil-derived IL-4, was attenuated in mice prophylactically treated with propolis. CONCLUSIONS: Taken together, these results demonstrate the ability of propolis to suppress IgE-dependent basophil activation and basophil-dependent allergic inflammation. Therefore, prophylactic treatment with propolis may be useful for protection against food allergic reactions in sensitive individuals. - Positive interactions between STAP-1 and BCR-ABL influence chronic myeloid leukemia cell proliferation and survival.
Marie Ishiura; Yuichi Kitai; Jun-Ichi Kashiwakura; Ryuta Muromoto; Jun Toda; Michiko Ichii; Kenji Oritani; Tadashi Matsuda
Biochemical and biophysical research communications, 556, 185, 191, 04 Jun. 2021, [International Magazine]
English, Scientific journal, Chronic myeloid leukemia (CML) is a clonal disease characterized by the presence of the Philadelphia chromosome and its oncogenic product, BCR-ABL, which activates multiple pathways involved in cell survival, growth promotion, and disease progression. We recently reported that signal-transducing adaptor protein 1 (STAP-1) is upregulated in CML stem cells (LSCs) and functions to reduce the apoptosis of CML LSCs by upregulating the STAT5-downstream anti-apoptotic genes. In this study, we demonstrate the detailed molecular interactions among BCR-ABL, STAP-1, and signal transducer and activator of transcription 5 (STAT5). Studies with deletion mutants have revealed that STAP-1 interacts with BCR-ABL and STAT5a through its SH2 and PH domains, respectively, suggesting the possible role of STAP-1 as a scaffold protein. Furthermore, the binding of STAP-1 to BCR-ABL stabilizes the BCR-ABL protein in CML cells. Since STAP-1 is highly expressed in CML cells, we also analyzed the STAP-1 promoter activity using a luciferase reporter construct and found that NFATc1 is involved in activating the STAP-1 promoter and inducing STAP-1 mRNA expression. Our results demonstrate that STAP-1 contributes to the BCR-ABL/STAT5 and BCR-ABL/Ca2+/NFAT signals to induce proliferation and STAP-1 mRNA expression in CML cells, respectively. - CD47 promotes T-cell lymphoma metastasis by up-regulating AKAP13-mediated RhoA activation.
Yuichi Kitai; Marie Ishiura; Kodai Saitoh; Naoki Matsumoto; Kimiya Owashi; Shunsuke Yamada; Ryuta Muromoto; Jun-Ichi Kashiwakura; Kenji Oritani; Tadashi Matsuda
International immunology, 33, 5, 273, 280, 22 Apr. 2021, [International Magazine]
English, Scientific journal, CD47, a 50 kDa transmembrane protein, facilitates integrin-mediated cell adhesion and inhibits cell engulfment by phagocytes. Since CD47 blocking promotes engulfment of cancer cells by macrophages, it is important to clarify the mechanism of CD47 signaling in order to develop treatments for diseases involving CD47-overexpressing cancer cells, including breast cancer and lymphoma. Here, we show that CD47 plays an essential role in T-cell lymphoma metastasis by up-regulating basal RhoA activity independent of its anti-phagocytic function. CD47 interacts with AKAP13, a RhoA-specific guanine nucleotide exchange factor (GEF), and facilitates AKAP13-mediated RhoA activation. Our study shows that CD47 has a novel function on the AKAP13-RhoA axis and suggests that CD47-AKAP13 interaction would be a novel target for T-cell lymphoma treatment. - Synthesis of Resolvin E1 and Its Conformationally Restricted Cyclopropane Congeners with Potent Anti-Inflammatory Effect
Kohei Ishimura; Hayato Fukuda; Koichi Fujiwara; Ryuta Muromoto; Koki Hirashima; Yuto Murakami; Mizuki Watanabe; Jun Ishihara; Tadashi Matsuda; Satoshi Shuto
ACS Medicinal Chemistry Letters, 12, 2, 256, 261, American Chemical Society (ACS), 11 Feb. 2021
Scientific journal - Therapeutic Advantage of Tyk2 Inhibition for Treating Autoimmune and Chronic Inflammatory Diseases.
Ryuta Muromoto; Kazuya Shimoda; Kenji Oritani; Tadashi Matsuda
Biological & pharmaceutical bulletin, 44, 11, 1585, 1592, 2021, [Domestic magazines]
English, Scientific journal, Tyrosine kinase 2 (Tyk2) is a member of the Janus family of protein tyrosine kinases (Jaks). Tyk2 associates with interferon (IFN)-α, IFN-β, interleukin (IL)-6, IL-10, IL-12, and IL-23 receptors and mediates their downstream signaling pathways. Based on our data using Tyk2-deficient mice and cells, Tyk2 plays crucial roles in the differentiation, maintenance, and function of T helper 1 (Th1) and Th17 cells, and its dysregulation may promote autoimmune and/or inflammatory diseases. IFN-α-induced growth inhibition of B lymphocyte progenitors is dependent on Tyk2-mediated signals to regulate death-associated protein (Daxx) nuclear localization and Daxx-promyelocytic leukemia protein interactions. Tyk2-deficient mice show impaired constitutive production of type I IFNs by macrophages under steady-state conditions. When heat-killed Cutibacterium acnes is injected intraperitoneally, Tyk2-deficient mice show less granuloma formation through enhanced prostaglandin E2 and protein kinase A activities, leading to high IL-10 production by macrophages. Thus, Tyk2 is widely involved in the immune and inflammatory response at multiple events; therefore, Tyk2 is likely to be a suitable target for treating patients with autoimmune and/or chronic inflammatory diseases. Clinical trials of Tyk2 inhibitors have shown higher response rates and improved tolerability in the treatment of patients with psoriasis and inflammatory bowel diseases. Taken together, Tyk2 inhibition has great potential for clinical application in the management of a variety of diseases. - Pivotal Role of Signal-Transducing Adaptor Protein-2 in Pathogenesis of Autoimmune Hepatitis.
Yuto Sasaki; Kodai Saitoh; Kota Kagohashi; Yuichi Kitai; Ryuta Muromoto; Kenji Oritani; Jun-Ichi Kashiwakura; Tadashi Matsuda
Biological & pharmaceutical bulletin, 44, 12, 1898, 1901, 2021, [Domestic magazines]
English, Scientific journal, Signal-transducing adaptor protein-2 (STAP-2) is an adaptor protein involved in inflammatory and immune responses, such as inflammatory bowel disease and allergic responses. In this study, we investigated the role of STAP-2 in the pathogenesis of autoimmune hepatitis. After intravenous injection of concanavalin A (ConA), STAP-2 knock out (KO) mice showed more severe liver necrosis along with substantial lymphocyte infiltration compared to wild type (WT) mice. Serum alanine aminotransferase levels were significantly higher in ConA-injected STAP-2 KO mice than in WT mice. Levels of interferon-γ (IFN-γ), an important factor for liver necrosis, were also significantly increased in sera of STAP-2 KO mice compared to WT mice after ConA injection. Statistically significant upregulation of Fas ligand (FasL) expression was observed in the livers of ConA-injected STAP-2 KO mice compared to WT mice. In accordance with these results, apoptotic signals were facilitated in STAP-2 KO mice compared to WT mice after ConA injection. Correctively, these results suggest that STAP-2 is involved in the pathogenesis of autoimmune hepatitis by regulating the expression of FasL and the production of IFN-γ. - Correction: Expression of signal-transducing adaptor protein-1 attenuates experimental autoimmune hepatitis via down-regulating activation and homeostasis of invariant natural killer T cells.
Jun-Ichi Kashiwakura; Kodai Saitoh; Takeru Ihara; Yuto Sasaki; Kota Kagohashi; Shiyo Enohara; Yuka Morioka; Hiroshi Watarai; Ryuta Muromoto; Yuichi Kitai; Kazuya Iwabuchi; Kenji Oritani; Tadashi Matsuda
PloS one, 16, 4, e0250536, 2021, [International Magazine]
English, [This corrects the article DOI: 10.1371/journal.pone.0241440.]. - Implication of NF-κB Activation on Ozone-Induced HO-1 Activation
Sumihito Togi; Misa Togi; Satoshi Nagashima; Yuichi Kitai; Ryuta Muromoto; Jun-ichi Kashiwakura; Toshiaki Miura; Tadashi Matsuda
BPB Reports, 4, 2, 59, 63, Pharmaceutical Society of Japan, 2021
Scientific journal - Graft-versus-host disease develops in mice transplanted with lymphocyte-depleted bone marrow cells from signal-transducing adaptor protein-2 transgenic mice
Hideaki Saito; Michiko Ichii; Jun Toda; Yuichi Kitai; Ryuta Muromoto; Jun-ichi Kashiwakura; Kodai Saitoh; Akira Tanimura; Takafumi Yokota; Hirohiko Shibayama; Tadashi Matsuda; Kenji Oritani; Yuzuru Kanakura; Naoki Hosen
Biochemical and Biophysical Research Communications, 537, 118, 124, Elsevier BV, Jan. 2021
Scientific journal - Expression of signal-transducing adaptor protein-1 attenuates experimental autoimmune hepatitis via down-regulating activation and homeostasis of invariant natural killer T cells
Jun-ichi Kashiwakura; Kodai Saitoh; Takeru Ihara; Yuto Sasaki; Kota Kagohashi; Shiyo Enohara; Yuka Morioka; Hiroshi Watarai; Ryuta Muromoto; Yuichi Kitai; Kazuya Iwabuchi; Kenji Oritani; Tadashi Matsuda
PLOS ONE, 15, 11, e0241440, e0241440, Public Library of Science (PLoS), 11 Nov. 2020
Scientific journal,Objective
Signal-transducing adaptor protein (STAP) family members function as adaptor molecules and are involved in several events during immune responses. Notably however, the biological functions of STAP-1 in other cells are not known. We aimed to investigate the functions of STAP-1 in invariant natural killer T (iNKT) cells and iNKT cell-dependent hepatitis.Methods
We employed concanavalin A (Con A)-induced hepatitis and α-galactosylceramide (α-GalCer)-induced hepatitis mouse models, both are models of iNKT cell-dependent autoimmune hepatitis, and STAP-1 overexpressing 2E10 cells to investigate the role of STAP-1 in iNKT cell activation in vivo an in vitro, respectively.Results
After Con A- or α-GalCer-injection, hepatocyte necrotic areas and plasma alanine aminotransferase elevation were more severe in STAP-1 knockout (S1KO) mice and milder in lymphocyte-specific STAP-1 transgenic (S1Tg) mice, as compared to wild-type (WT) mice. Two events that may be related to Con A-induced and/or α-GalCer-induced hepatitis were influenced by STAP-1 manipulation. One is that iNKT cell populations in the livers and spleens were increased in S1KO mice and were decreased in S1Tg mice. The other is that Con A-induced interleukin-4 and interferon-γ production was attenuated by STAP-1 overexpression. These effects of STAP-1 were confirmed using 2E10 cells overexpressing STAP-1 that showed impairment of interleukin-4 and interferon-γ production as well as phosphorylation of Akt and mitogen-activated protein kinases in response to Con A stimulation.Conclusions
These results conclude that STAP-1 regulates iNKT cell maintenance/activation, and is involved in the pathogenesis of autoimmune hepatitis. - Synthesis of Resolvin E3, a Proresolving Lipid Mediator, and Its Deoxy Derivatives: Identification of 18-Deoxy-resolvin E3 as a Potent Anti-Inflammatory Agent
Hayato Fukuda; Hiroyuki Ikeda; Ryuta Muromoto; Koki Hirashima; Kohei Ishimura; Koichi Fujiwara; Haruka Aoki-Saito; Takeshi Hisada; Mizuki Watanabe; Jun Ishihara; Tadashi Matsuda; Satoshi Shuto
The Journal of Organic Chemistry, 85, 21, 14190, 14200, American Chemical Society (ACS), 06 Nov. 2020
Scientific journal - Signal-transducing adapter protein-1 is required for maintenance of leukemic stem cells in CML.
Jun Toda; Michiko Ichii; Kenji Oritani; Hirohiko Shibayama; Akira Tanimura; Hideaki Saito; Takafumi Yokota; Daisuke Motooka; Daisuke Okuzaki; Yuichi Kitai; Ryuta Muromoto; Jun-Ichi Kashiwakura; Tadashi Matsuda; Naoki Hosen; Yuzuru Kanakura
Oncogene, 39, 34, 5601, 5615, 13 Jul. 2020, [Peer-reviewed], [International Magazine]
English, Scientific journal, The family of signal-transducing adapter proteins (STAPs) has been reported to be involved in a variety of intracellular signaling pathways and implicated as transcriptional factors. We previously cloned STAP-2 as a c-Fms interacting protein and explored its effects on chronic myeloid leukemia (CML) leukemogenesis. STAP-2 binds to BCR-ABL, upregulates BCR-ABL phosphorylation, and activates its downstream molecules. In this study, we evaluated the role of STAP-1, another member of the STAP family, in CML pathogenesis. We found that the expression of STAP-1 is aberrantly upregulated in CML stem cells (LSCs) in patients' bone marrow. Using experimental model mice, deletion of STAP-1 prolonged the survival of CML mice with inducing apoptosis of LSCs. The impaired phosphorylation status of STAT5 by STAP-1 ablation leads to downregulation of antiapoptotic genes, Bcl-2 and Bcl-xL. Interestingly, transcriptome analyses indicated that STAP-1 affects several signaling pathways related to BCR-ABL, JAK2, and PPARγ. This adapter protein directly binds to not only BCR-ABL, but also STAT5 proteins, showing synergistic effects of STAP-1 inhibition and BCR-ABL or JAK2 tyrosine kinase inhibition. Our results identified STAP-1 as a regulator of CML LSCs and suggested it to be a potential therapeutic target for CML. - The mechanism of Tyk2 deficiency-induced immunosuppression in mice involves robust IL-10 production in macrophages
Hirashima K; Muromoto R; Minoguchi H; Matsumoto T; Kitai Y; Kashiwakura JI; Shimoda K; Oritani K; Matsuda T
Cytokine, 130, 155077, 155077, Jun. 2020, [Peer-reviewed], [International Magazine]
English, Scientific journal, Macrophages are highly plastic in their pro-inflammatory/anti-inflammatory roles. Type I and II interferons (IFNs) are known to modulate macrophage activation. Tyrosine kinase 2 (Tyk2) has an intimate relationship with type I and II IFN signaling. Animal studies have shown that Tyk2 knock-out (KO) in mice is associated with reduced inflammatory responses in various mouse models of diseases. To investigate the role of Tyk2 in inflammation in more detail, we intraperitoneally injected heat-killed Propionibacterium acnes (P. acnes) to Tyk2 KO mice. P. acnes-induced acute peritoneal inflammation, assessed by neutrophil infiltration, was reduced in Tyk2 KO mice. The reduction was accompanied with diminished productions of inflammatory cytokines and an enhanced production of anti-inflammatory IL-10. Unexpectedly, pre-treatment of wild-type mice with the neutralizing antibodies for IFNs did not affect P. acnes-induced neutrophil infiltration. A neutralizing antibody for the IL-10 receptor in Tyk2 KO mice restored P. acnes-induced peritoneal inflammation. Enhanced production of IL-10 from Tyk2 KO peritoneal cells was suppressed by either the cyclooxygenase inhibitor diclofenac or protein kinase A inhibitor H-89. The level of prostaglandin E2 (PGE2) in the steady-state peritoneal cavity in Tyk2 KO mice was higher than that in wild-type mice. Tyk2 KO macrophages showed an enhanced CREB phosphorylation induced by P. acnes plus PGE2. Taken together, these results showed that Tyk2 deficiency potentiates the PGE2-protein kinase A-IL-10 pathway in macrophages, and thereby contributes to potentiation of the immunosuppressive phenotype. - Design and Synthesis of Benzene Congeners of Resolvin E2, a Proresolving Lipid Mediator, as Its Stable Equivalents
Yuto Murakami; Hayato Fukuda; Ryuta Muromoto; Koki Hirashima; Kohei Ishimura; Koichi Fujiwara; Jun Ishihara; Tadashi Matsuda; Mizuki Watanabe; Satoshi Shuto
ACS MEDICINAL CHEMISTRY LETTERS, 11, 4, 479, 484, Apr. 2020, [Peer-reviewed]
English, Scientific journal - Tyk2欠損マウスにおける免疫反応抑制にはマクロファージでのIL-10産生増強が関与する
室本 竜太; 平島 洸基; 美濃口 広弥; 松田 正
日本薬学会年会要旨集, 140年会, 26Z, am13, (公社)日本薬学会, Mar. 2020
Japanese - Signal-transducing adaptor protein-2 delays recovery of B lineage lymphocytes during hematopoietic stress.
Michiko Ichii; Kenji Oritani; Jun Toda; Hideaki Saito; Henyun Shi; Hirohiko Shibayama; Daisuke Motooka; Yuichi Kitai; Ryuta Muromoto; Jun-Ichi Kashiwakura; Kodai Saitoh; Daisuke Okuzaki; Tadashi Matsuda; Yuzuru Kanakura
Haematologica, 106, 2, 424, 436, 23 Jan. 2020, [Peer-reviewed], [International Magazine]
English, Scientific journal, Signal-transducing adaptor protein-2 (STAP-2) was discovered as a C-FMS/M-CSFR interacting protein and subsequently found to function as an adaptor of signaling or transcription factors. These include STAT5, MyD88 and IκB kinase in macrophages, mast cells, and T cells. There is additional information about roles for STAP-2 in several types of malignant diseases including chronic myeloid leukemia, however, none have been reported concerning B lineage lymphocytes. We have now exploited gene targeted and transgenic mice to address this lack of knowledge, and demonstrated that STAP-2 is not required under normal, steady-state conditions. However, recovery of B cells following transplantation was augmented in the absence of STAP-2. This appeared to be restricted to cells of B cell lineage with myeloid rebound noted as unremarkable. Furthermore, all hematological parameters were observed to be normal once recovery from transplantation was complete. Furthermore, overexpression of STAP-2, specifically in lymphoid cells, resulted in reduced numbers of late-stage B cell progenitors within the bone marrow. While numbers of mature peripheral B and T cells were unaffected, recovery from sub-lethal irradiation or transplantation was dramatically reduced. Lipopolysaccharide (LPS) normally suppresses B precursor expansion in response to interleukin 7, however, STAP-2 deficiency made these cells more resistant. Preliminary RNA-Seq analyses indicated multiple signaling pathways in B progenitors as STAP-2-dependent. These findings suggest that STAP-2 modulates formation of B lymphocytes in demand conditions. Further study of this adapter protein could reveal ways to speed recovery of humoral immunity following chemotherapy or transplantation. - Dimethyl fumarate dampens IL-17-ACT1-TBK1 axis-mediated phosphorylation of Regnase-1 and suppresses IL-17-induced IκB-ζ expression.
Ohgakiuchi Y; Saino Y; Muromoto R; Komori Y; Sato A; Hirashima K; Kitai Y; Kashiwakura JI; Oritani K; Matsuda T
Biochemical and biophysical research communications, 521, 4, 957, 963, Nov. 2019, [Peer-reviewed], [International Magazine]
English, Scientific journal, The signaling elicited by the cytokine interleukin-17A (IL-17) is important for antimicrobial defense responses, whereas excessive IL-17 production leads to autoimmune diseases such as psoriasis and multiple sclerosis. IL-17-induced stabilization of mRNAs has been recognized as a unique and important feature of IL-17 signaling. Previously, we demonstrated that IL-17 signaling protein ACT1 is required to counteract constitutive inhibitor of nuclear factor kappa B zeta (IκB-ζ) mRNA degradation by the ribonuclease Regnase-1. However, information about the mechanism of mRNA stabilization in IL-17-stimulated cells remains insufficient. In the present study, we aimed to clarify the mechanism in more detail and identify an agent that can inhibit IL-17-induced mRNA stabilization. Experiments using small interfering RNA and an inhibitor of TANK-binding kinase 1 (TBK1) revealed that TBK1 was required for IκB-ζ mRNA stabilization through Regnase-1 phosphorylation. Intriguingly, this TBK1-mediated phosphorylation of Regnase-1 was suppressed by the addition of dimethyl fumarate (DMF), an electrophilic small molecule that has been used to treat IL-17-related autoimmune diseases. Confocal microscopic observation of the cellular localization of ACT1 revealed that DMF treatment resulted in the disappearance of ACT1 nuclear dots and perinuclear accumulation of ACT1. These results suggested that DMF is a small molecule that compromises IL-17-induced activation of the ACT1-TBK1 pathway, thereby inhibiting IL-17-induced mRNA stabilization. - The basophil-IL-4-mast cell axis is required for food allergy.
Jun-Ichi Kashiwakura; Tomoaki Ando; Hajime Karasuyama; Masato Kubo; Kenji Matsumoto; Tadashi Matsuda; Toshiaki Kawakami
Allergy, 74, 10, 1992, 1996, Oct. 2019, [Peer-reviewed], ［Internationally co-authored］, [International Magazine]
English, Scientific journal - IκB-ζ Expression Requires Both TYK2/STAT3 Activity and IL-17-Regulated mRNA Stabilization.
Muromoto R; Tawa K; Ohgakiuchi Y; Sato A; Saino Y; Hirashima K; Minoguchi H; Kitai Y; Kashiwakura JI; Shimoda K; Oritani K; Matsuda T
ImmunoHorizons, 3, 5, 172, 185, May 2019, [Peer-reviewed], [International Magazine]
English, Scientific journal, Cytokine IL-17A (IL-17) acts on various cell types, including epidermal keratinocytes, and induces antimicrobial peptide and chemokine production to elicit antibacterial and antifungal defense responses. Excess IL-17 leads to inflammatory skin diseases such as psoriasis. The IκB family protein IκB-ζ mediates IL-17-induced responses. However, the mechanism controlling IκB-ζ expression in IL-17-stimulated cells remains elusive. In this study, we showed that JAK kinase TYK2 positively regulates IL-17-induced IκB-ζ expression. TYK2-deficient mice showed reduced inflammation and concomitant reduction of IκB-ζ mRNA compared with wild-type mice in imiquimod-induced skin inflammation. The analysis of the IκB-ζ promoter activity using human cell lines (HaCaT and HeLa) revealed that catalytic activity of TYK2 and its substrate transcription factor STAT3, but not IL-17, is required for IκB-ζ promoter activity. In contrast, IL-17-induced signaling, which did not activate STAT3, posttranscriptionally stabilized IκB-ζ mRNA via its 3'-untranslated region. IL-17 signaling protein ACT1 was required to counteract constitutive IκB-ζ mRNA degradation by RNase Regnase-1. These results suggested that transcriptional activation by TYK2-STAT3 pathway and mRNA stabilization by IL-17-mediated signals act separately from each other but complementarily to achieve IκB-ζ induction. Therefore, JAK/TYK2 inhibition might be of significance in regulation of IL-17-induced inflammatory reactions. - STAP-2 positively regulates FcRI-mediated basophil activation and basophil-dependent allergic inflammatory reaction.
Kashiwakura JI; Yamashita S; Yoshihara M; Inui K; Saitoh K; Sekine Y; Muromoto R; Kitai Y; Oritani K; Matsuda T
International immunology, 31, 5, 349, 356, Feb. 2019, [Peer-reviewed], ［Internationally co-authored］, [International Magazine]
English, Scientific journal, Basophils are an important cell type in the regulation of Th2 immune responses. Recently, we revealed that signal-transducing adaptor protein-2 (STAP-2) negatively regulates mast cell activation via FcεRI. However, the role of STAP-2 in basophil maturation and activation remained unclear. In this study, we demonstrated the normal development of basophils in STAP-2-deficient (STAP-2-/-) mice. We also demonstrated in vitro normal basophil differentiation and FcεRI expression in STAP-2-/- mice, suggesting that STAP-2 is dispensable for basophil maturation. Using bone marrow-derived cultured basophils (BMBs), we showed that degranulation and cytokine production of STAP-2-/- BMBs were lower than those of wild-type (WT) BMBs upon stimulation with IgE/Ag. In accordance with the reduction of degranulation and cytokine production, phosphorylation of several signal molecules such as Lyn, PLC-γ2 and Erk was reduced in STAP-2-/- BMBs after stimulation via FcεRI. Finally, it was observed that IgE-dependent chronic allergic inflammation of STAP-2-/- mice was significantly inhibited compared with WT mice. Taken together, we conclude that STAP-2 is an adaptor molecule that positively regulates FcεRI-mediated basophil activation and basophil-dependent allergic inflammatory reactions. - A Novel α9 Integrin Ligand, XCL1/Lymphotactin,Is Involved in the Development of Murine Models of Autoimmune Diseases
松本, 尚樹; 今, 重之; 中鶴, 拓也; 宮下, 友惠; 乾, 恭輔; 齋藤, 浩大; 鍛代, 悠—; 室本, 竜太; 柏倉, 淳一; 上出, 利光; 松田, 正
Annual report of the Faculty of Pharmacy & Pharmaceutical Sciences, Fukuyama University, 36, 50, 51, 福山大学薬学部, 25 Dec. 2018
Japanese, Research institution - Signal Transducing Adaptor Protein (STAP) Family Accelerates Gut and Thymic Graft-Versus-Host-Disease in Murine Model.
Hideaki Saito; Michiko Ichii; Jun Toda; Yuichi Kitai; Ryuta Muromoto; Jun-ichi Kashiwakura; Kodai Saitoh; Hirohiko Shibayama; Tadashi Matsuda; Kenji Oritani; Yuzuru Kanakura
The American Society of Hematology 60th Annual Meeting, Dec. 2018, [Peer-reviewed]
English - Signal transducing adaptor protein-2(STAP-2)はマウスモデルで慢性GVHDを悪化させる
西東秀晃; 一井倫子; 戸田 淳; 鍛代悠一; 室本竜太; 柏倉淳一; 齋藤浩大; 柴山浩彦; 松田 正; 織谷健司; 金倉 譲
第80回日本血液学会学術集会, Oct. 2018, [Peer-reviewed]
Japanese, Research society - 慢性骨髄性白血病におけるSTAPファミリー蛋白の役割
戸田 淳; 一井倫子; 西東秀晃; 鍛代悠一; 室本竜太; 柏倉淳一; 齋藤浩大; 柴山浩彦; 松田 正; 織谷健司; 金倉 譲
第80回日本血液学会学術集会, Oct. 2018, [Peer-reviewed]
Japanese, Research society - 骨髄内B細胞分化におけるSTAP-2蛋白の役割
一井倫子; 織谷健司; 柴山浩彦; 戸田 淳; 西東秀晃; 北井勇一; 室本竜太; 柏倉淳一; 齋藤浩大; 松田 正; 金倉 譲
第80回日本血液学会学術集会, Oct. 2018, [Peer-reviewed]
Japanese - 慢性骨髄性白血病におけるSTAPファミリー蛋白の役割(Roles of signal trandsducing adaptor proteins in the pathogenesis of chronic myelogenous leukemia)
戸田 淳; 一井 倫子; 西東 秀晃; 鍛代 悠一; 室本 竜太; 柏倉 淳一; 齋藤 浩大; 柴山 浩彦; 松田 正; 織谷 健司; 金倉 譲
臨床血液, 59, 9, 1531, 1531, (一社)日本血液学会-東京事務局, Sep. 2018
English - Signal transducing adaptor protein-2(STAP-2)はマウスモデルで慢性GVHDを悪化させる(Signal transducing adaptor protein-2, STAP-2 accelerates chronic GVHD in murine mouse model)
西東 秀晃; 一井 倫子; 戸田 淳; 鍛代 悠一; 室本 竜太; 柏倉 淳一; 齋藤 浩大; 柴山 浩彦; 松田 正; 織谷 健司; 金倉 譲
臨床血液, 59, 9, 1545, 1545, (一社)日本血液学会-東京事務局, Sep. 2018
English - 骨髄内B細胞分化におけるSTAP-2蛋白の役割(Signal-transducing adaptor protein-2 regulates humoral immune reconstitution at pre-B stage)
一井 倫子; 織谷 健司; 柴山 浩彦; 戸田 淳; 西東 秀晃; 北井 勇一; 室本 竜太; 柏倉 淳一; 齋藤 浩大; 松田 正; 金倉 譲
臨床血液, 59, 9, 1695, 1695, (一社)日本血液学会-東京事務局, Sep. 2018
English - Synthesis of Chiral cis-Cyclopropane Bearing Indole and Chromone as Potential TNFα Inhibitors
Ryutaro Kanada; Makoto Tanabe; Ryuta Muromoto; Yukina Sato; Tomoki Kuwahara; Hayato Fukuda; Mitsuhiro Arisawa; Tadashi Matsuda; Mizuki Watanabe; Satoshi Shuto
Journal of Organic Chemistry, 83, 15, 7672, 7682, 03 Aug. 2018, [Peer-reviewed]
Scientific journal - 新規α4インテグリンスプライシングバリアントは内在性α4インテグリン抑制分子である
重政 歩美; 乾 恭輔; 本田 真知子; 松田 正; 今 重之
日本薬学会年会要旨集, 138年会, 3, 72, 72, (公社)日本薬学会, Mar. 2018
Japanese - 自己免疫疾患における細胞外基質ネフロネクチンの関与
藤岡 和征; 本田 真知子; 松田 正; 今 重之
日本薬学会年会要旨集, 138年会, 3, 72, 72, (公社)日本薬学会, Mar. 2018
Japanese - 細胞外基質ネフロネクチンに対するサンドイッチELISAシステムの構築
本田 真知子; 李 順姫; 松田 正; 大槻 剛巳; 今 重之
日本薬学会年会要旨集, 138年会, 3, 73, 73, (公社)日本薬学会, Mar. 2018
Japanese - A new STAT3-binding partner, ARL3, enhances the phosphorylation and nuclear accumulation of STAT3
硎, 澄仁; 室本, 竜太; 平島, 洸基; 鍛代, 悠—; 岡山, 太一郎; 池田, 収; 松本, 尚樹; 今, 重之; 関根, 勇—; 織谷, 健司; 松田, 正
Annual report of the Faculty of Pharmacy & Pharmaceutical Sciences, Fukuyama University, 35, 53, 53, 福山大学薬学部, 25 Dec. 2017
Japanese, Research institution - Anti-IL-17 A blocking antibody reduces cyclosporinA-induced relapse in experimental autoimmune encephalomyelitis mice.
齋藤, 浩大; 今, 重之; 中鶴, 拓也; 乾, 恭輔; 伊原, 建; 松本, 尚樹; 鍛代, 悠—; 室本, 竜太; 松田, 正
Annual report of the Faculty of Pharmacy & Pharmaceutical Sciences, Fukuyama University, 35, 54, 54, 福山大学薬学部, 25 Dec. 2017
Japanese, Research institution - STAP-2 protein promotes prostate cancer growth by enhancing epidermal growth factor receptor stabilization
Yuichi Kitai; Masashi Iwakami; Kodai Saitoh; Sumihito Togi; Serina Isayama; Yuichi Sekine; Ryuta Muromoto; Jun-ichi Kashiwakura; Akihiko Yoshimura; Kenji Oritani; Tadashi Matsuda
JOURNAL OF BIOLOGICAL CHEMISTRY, 292, 47, 19392, 19399, Nov. 2017, [Peer-reviewed]
English, Scientific journal - Biochanin A enhances ROR gamma activity through STAT3-mediated recruitment of NCOA1
Miki Takahashi; Ryuta Muromoto; Hiroyuki Kojima; Shinji Takeuchi; Yuichi Kitai; Jun-ichi Kashiwakura; Tadashi Matsuda
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 489, 4, 503, 508, Aug. 2017, [Peer-reviewed]
English, Scientific journal - A Novel alpha 9 Integrin Ligand, XCL1/Lymphotactin, Is Involved in the Development of Murine Models of Autoimmune Diseases
Naoki Matsumoto; Shigeyuki Kon; Takuya Nakatsuru; Tomoe Miyashita; Kyosuke Inui; Kodai Saitoh; Yuichi Kitai; Ryuta Muromoto; Jun-ichi Kashiwakura; Toshimitsu Uede; Tadashi Matsuda
JOURNAL OF IMMUNOLOGY, 199, 1, 82, 90, Jul. 2017, [Peer-reviewed]
English, Scientific journal - STAP-2 interacts with Pyk2 and enhances Pyk2 activity in T-cells
Kodai Saitoh; Takuya Tsuchiya; Jun-ichi Kashiwakura; Ryuta Muromoto; Yuichi Kitai; Yuichi Sekine; Kenji Oritani; Tadashi Matsuda
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 488, 1, 81, 87, Jun. 2017, [Peer-reviewed]
English, Scientific journal - Dupuytren拘縮における線維化メカニズムの解析
松井 雄一郎; 今 重之; 船越 忠直; 松田 正; 岩崎 倫政
日本手外科学会雑誌, 34, 1, S207, S207, (一社)日本手外科学会, Apr. 2017
Japanese - Dupuytren拘縮における線維化メカニズムの解析
松井 雄一郎; 船越 忠直; 河村 太介; 亀田 裕亮; 岩崎 倫政; 今 重之; 宮下 友恵; 松田 正
北海道整形災害外科学会雑誌, 58, 2, 302, 302, 北海道整形災害外科学会, Mar. 2017
Japanese - DNA-Containing Exosomes Derived from Cancer Cells Treated with Topotecan Activate a STING- Dependent Pathway and Reinforce Antitumor Immunity
Yuichi Kitai; Takumi Kawasaki; Takuya Sueyoshi; Kouji Kobiyama; Ken J. Ishii; Jian Zou; Shizuo Akira; Tadashi Matsuda; Taro Kawai
JOURNAL OF IMMUNOLOGY, 198, 4, 1649, 1659, Feb. 2017, [Peer-reviewed]
English, Scientific journal - Increased expression of v integrin as a regulator of fibrosis in Dupuytren's nodules
Y. Matsui; S. Kon; T. Funakoshi; T. Miyashita; T. Matsuda; N. Iwasaki
JOURNAL OF HAND SURGERY-EUROPEAN VOLUME, 42, 1, 18, 25, Jan. 2017, [Peer-reviewed]
English, Scientific journal - Design and Synthesis of Cyclopropane Congeners of Resolvin E2, an Endogenous Proresolving Lipid Mediator, as Its Stable Equivalents
Hayato Fukuda; Ryuta Muromoto; Yuuki Takakura; Kohei Ishimura; Ryutaro Kanada; Daichi Fushihara; Makoto Tanabe; Kotaro Matsubara; Toru Hirao; Koki Hirashima; Hiroshi Abe; Mitsuhiro Arisawa; Tadashi Matsuda; Satoshi Shuto
Organic Letters, 18, 24, 6224, 6227, 16 Dec. 2016, [Peer-reviewed]
Scientific journal - Anti-IL-17A blocking antibody reduces cyclosporin A-induced relapse in experimental autoimmune encephalomyelitis mice.
Kodai Saitoh; Shigeyuki Kon; Takuya Nakatsuru; Kyosuke Inui; Takeru Ihara; Naoki Matsumoto; Yuichi Kitai; Ryuta Muromoto; Tadashi Matsuda
Biochemistry and biophysics reports, 8, 139, 145, Dec. 2016, [Peer-reviewed], [International Magazine]
English, Scientific journal, Cyclosporin A (CsA) is effective at reducing pathogenic immune responses, but upon withdrawal of CsA the immune response often "rebounds" resulting in a relapse or exacerbation of disease. The mechanisms, cells and cytokines involved in the relapse or exacerbation after CsA withdrawal are unknown. We hypothesized that CsA withdrawal induces IL-17 production that could be responsible for relapse, and examined the effect of anti-IL-17A antibody on relapse induced after CsA withdrawal in mouse experimental autoimmune encephalomyelitis (EAE). CsA treatment markedly decreased the EAE disease score during the first episode, but augmented disease severity after CsA withdrawal, compared to untreated mice. After discontinuation of CsA the production of IL-17A was increased and the severity of relapse in EAE was reduced by treatment with anti-IL-17A antibody. These results suggest that the resumption of T cell immune responses after CsA withdrawal leads to a burst of IL-17A production that is at least partially responsible for relapse in EAE mice. - The immunosuppressive effect of domain-deleted dimer of HLA-G2 isoform in collagen-induced arthritis mice
Ami Takahashi; Kimiko Kuroki; Yuki Okabe; Yoshiyuki Kasai; Naoki Matsumoto; Chisato Yamada; Toshiyuki Takai; Toyoyuki Ose; Shigeyuki Kon; Tadashi Matsuda; Katsumi Maenaka
HUMAN IMMUNOLOGY, 77, 9, 754, 759, Sep. 2016, [Peer-reviewed]
English, Scientific journal - IL-17A plays a central role in the expression of psoriasis signature genes through the induction of I kappa B-zeta in keratinocytes
Ryuta Muromoto; Toru Hirao; Keisuke Tawa; Koki Hirashima; Shigeyuki Kon; Yuichi Kitai; Tadashi Matsuda
INTERNATIONAL IMMUNOLOGY, 28, 9, 443, 452, Sep. 2016, [Peer-reviewed]
English, Scientific journal - A New STAT3-binding Partner, ARL3, Enhances the Phosphorylation and Nuclear Accumulation of STAT3.
Sumihito Togi; Ryuta Muromoto; Koki Hirashima; Yuichi Kitai; Taichiro Okayama; Osamu Ikeda; Naoki Matsumoto; Shigeyuki Kon; Yuichi Sekine; Kenji Oritani; Tadashi Matsuda
The Journal of biological chemistry, 291, 21, 11161, 71, 20 May 2016, [Peer-reviewed], ［Internationally co-authored］, [International Magazine]
English, Scientific journal, Signal transducer and activator of transcription 3 (STAT3) is involved in cell proliferation, differentiation, and cell survival during immune responses, hematopoiesis, neurogenesis, and other biological processes. STAT3 activity is regulated by a variety of mechanisms, including phosphorylation and nuclear translocation. To clarify the molecular mechanisms underlying the regulation of STAT3 activity, we performed yeast two-hybrid screening. We identified ARL3 (ADP-ribosylation factor-like 3) as a novel STAT3-binding partner. ARL3 recognizes the DNA-binding domain as well as the C-terminal region of STAT3 in vivo, and their binding was the strongest when both proteins were activated. Importantly, small interfering RNA-mediated reduction of endogenous ARL3 expression decreased IL-6-induced tyrosine phosphorylation, nuclear accumulation, and transcriptional activity of STAT3. These results indicate that ARL3 interacts with STAT3 and regulates the transcriptional activation of STAT3 by influencing its nuclear accumulation of STAT3. - Dupuytren拘縮におけるインテグリンの関与
松井 雄一郎; 船越 忠直; 瓜田 淳; 河村 太介; 佃 幸憲; 岩崎 倫政; 今 重之; 松田 正
北海道整形災害外科学会雑誌, 57, 2, 288, 288, 北海道整形災害外科学会, Apr. 2016
Japanese - Dupuytren拘縮の最前線 Dupuytren拘縮の進行におけるインテグリンαvの関与
松井 雄一郎; 今 重之; 船越 忠直; 河村 太介; 亀田 裕亮; 宮下 友恵; 松田 正; 岩崎 倫政
日本整形外科学会雑誌, 90, 2, S379, S379, (公社)日本整形外科学会, Mar. 2016
Japanese - Caspase-dependent cleavage regulates protein levels of Epstein-Barr virus-derived latent membrane protein 1
Sumihito Togi; Yosuke Hatano; Ryuta Muromoto; Eri Kawanishi; Osamu Ikeda; Koki Hirashima; Shigeyuki Kon; Yuichi Kitai; Teruhito Yasui; Kenji Oritani; Tadashi Matsuda
FEBS LETTERS, 590, 6, 808, 818, Mar. 2016, [Peer-reviewed]
English, Scientific journal - α9インテグリンバリアントSFα9結合分子に着目した新規自己免疫疾患治療薬の開発
松本 尚樹; 中鶴 拓也; 宮下 友惠; 今 重之; 松田 正
日本生化学会大会・日本分子生物学会年会合同大会講演要旨集, 88回・38回, [1P0081], [1P0081], (公社)日本生化学会, Dec. 2015
Japanese - β8インテグリンスプライシングバリアントは新規TGF-βシグナル制御分子である
宮下 友惠; 今 重之; 中鶴 拓也; 松本 尚樹; 松井 雄一郎; 岩崎 倫政; 松田 正
日本生化学会大会・日本分子生物学会年会合同大会講演要旨集, 88回・38回, [1P0082], [1P0082], (公社)日本生化学会, Dec. 2015
Japanese - 自己免疫疾患における新規カルシウム結合タンパク質、ネフロネクチンの役割
中鶴 拓也; 今 重之; 宮下 友惠; 松本 尚樹; 乾 恭輔; 石川 清; 瀬川 辰也; 前田 雅弘; 松田 正
日本生化学会大会・日本分子生物学会年会合同大会講演要旨集, 88回・38回, [1P0084], [1P0084], (公社)日本生化学会, Dec. 2015
Japanese - T細胞活性化におけるSTAP-1及びSTAP-2の役割
齋藤 浩大; 今 重之; 小澤 清貴; 伊原 建; 関根 勇一; 室本 竜太; 鍛代 悠一; 吉村 昭彦; 織谷 健司; 松田 正
日本生化学会大会・日本分子生物学会年会合同大会講演要旨集, 88回・38回, [3T特, 02(3P1126)], (公社)日本生化学会, Dec. 2015
Japanese - Signal transducer and activator of transcription 3 regulation by novel binding partners.
Tadashi Matsuda; Ryuta Muromoto; Yuichi Sekine; Sumihito Togi; Yuichi Kitai; Shigeyuki Kon; Kenji Oritani
World journal of biological chemistry, 6, 4, 324, 32, 26 Nov. 2015, [Peer-reviewed], [International Magazine]
English, Scientific journal, Signal transducers and activators of transcription (STATs) mediate essential signals for various biological processes, including immune responses, hematopoiesis, and neurogenesis. STAT3, for example, is involved in the pathogenesis of various human diseases, including cancers, autoimmune and inflammatory disorders. STAT3 activation is therefore tightly regulated at multiple levels to prevent these pathological conditions. A number of proteins have been reported to associate with STAT3 and regulate its activity. These STAT3-interacting proteins function to modulate STAT3-mediated signaling at various steps and mediate the crosstalk of STAT3 with other cellular signaling pathways. This article reviews the roles of novel STAT3 binding partners such as DAXX, zipper-interacting protein kinase, Krüppel-associated box-associated protein 1, Y14, PDZ and LIM domain 2 and signal transducing adaptor protein-2, in the regulation of STAT3-mediated signaling. - CCR7 is involved in BCR-ABL/STAP-2-mediated cell growth in hematopoietic Ba/F3 cells
Kaori Kubo; Masashi Iwakami; Ryuta Muromoto; Takuya Inagaki; Yuichi Kitai; Shigeyuki Kon; Yuichi Sekine; Kenji Oritani; Tadashi Matsuda
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 463, 4, 825, 831, Aug. 2015, [Peer-reviewed]
English, Scientific journal - STAP-2 Protein Expression in B16F10 Melanoma Cells Positively Regulates Protein Levels of Tyrosinase, Which Determines Organs to Infiltrate in the Body
Yuichi Sekine; Sumihito Togi; Ryuta Muromoto; Shigeyuki Kon; Yuichi Kitai; Akihiko Yoshimura; Kenji Oritani; Tadashi Matsuda
JOURNAL OF BIOLOGICAL CHEMISTRY, 290, 28, 17462, 17473, Jul. 2015, [Peer-reviewed]
English, Scientific journal - Kaposi's sarcoma-associated herpesvirus-encoded LANA associates with glucocorticoid receptor and enhances its transcriptional activities
Sumihito Togi; Misa Nakasuji; Ryuta Muromoto; Osamu Ikeda; Kanako Okabe; Yuichi Kitai; Shigeyuki Kon; Kenji Oritani; Tadashi Matsuda
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 463, 3, 395, 400, Jul. 2015, [Peer-reviewed]
English, Scientific journal - PML suppresses IL-6-induced STAT3 activation by interfering with STAT3 and HDAC3 interaction
Masaya Kato; Ryuta Muromoto; Sumihito Togi; Masashi Iwakami; Yuichi Kitai; Shigeyuki Kon; Kenji Oritani; Tadashi Matsuda
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 461, 2, 366, 371, May 2015, [Peer-reviewed]
English, Scientific journal - 新規α9インテグリンリガンドLymphotactinの同定と機能解析
中鶴 拓也; 松本 尚樹; 紅露 ひとみ; 松田 正; 今 重之
日本薬学会年会要旨集, 135年会, 3, 95, 95, (公社)日本薬学会, Mar. 2015
Japanese - T細胞受容体シグナルにおけるSTAP-1及びSTAP-2の役割
小澤 清貴; 齋藤 浩大; 安次富 大; 関根 勇一; 室本 竜太; 今 重之; 松田 正
日本薬学会年会要旨集, 135年会, 3, 96, 96, (公社)日本薬学会, Mar. 2015
Japanese - Isoflavones enhance interleukin-17 gene expression via retinoic acid receptor-related orphan receptors alpha and gamma
Hiroyuki Kojima; Yukimasa Takeda; Ryuta Muromoto; Miki Takahashi; Toru Hirao; Shinji Takeuchi; Anton M. Jetten; Tadashi Matsuda
TOXICOLOGY, 329, 32, 39, Mar. 2015, [Peer-reviewed], ［Internationally co-authored］
English, Scientific journal - Signal-transducing adaptor protein-2 regulates macrophage migration into inflammatory sites during dextran sodium sulfate induced colitis
Natsuko Fujita; Kenji Oritani; Michiko Ichii; Takafumi Yokota; Norimitsu Saitoh; Daisuke Okuzaki; Yuichi Sekine; Shigeyuki Kon; Ryuta Muromoto; Kodai Saitoh; Akihiko Yoshimura; Tadashi Matsuda; Yuzuru Kanakura
EUROPEAN JOURNAL OF IMMUNOLOGY, 44, 6, 1791, 1801, Jun. 2014, [Peer-reviewed]
English, Scientific journal - The Novel alpha 4B Murine alpha 4 Integrin Protein Splicing Variant Inhibits alpha 4 Protein-dependent Cell Adhesion
Hitomi Kouro; Shigeyuki Kon; Naoki Matsumoto; Tomoe Miyashita; Ayaka Kakuchi; Dai Ashitomi; Kodai Saitoh; Takuya Nakatsuru; Sumihito Togi; Ryuta Muromoto; Tadashi Matsuda
JOURNAL OF BIOLOGICAL CHEMISTRY, 289, 23, 16389, 16398, Jun. 2014, [Peer-reviewed]
English, Scientific journal - Tyk2 is a therapeutic target for psoriasis-like skin inflammation
Masayuki Ishizaki; Ryuta Muromoto; Toshihiko Akimoto; Yuichi Sekine; Shigeyuki Kon; Manish Diwan; Hiroaki Maeda; Sumihito Togi; Kazuya Shimoda; Kenji Oritani; Tadashi Matsuda
INTERNATIONAL IMMUNOLOGY, 26, 5, 257, 267, May 2014, [Peer-reviewed]
English, Scientific journal - Promoter Hypermethylation of the Phosphatase DUSP22 Mediates PKA- Dependent TAU Phosphorylation and CREB Activation in Alzheimer's Disease
Jose Vicente Sanchez-Mut; Ester Aso; Holger Heyn; Tadashi Matsuda; Christoph Bock; Isidre Ferrer; Manel Esteller
HIPPOCAMPUS, 24, 4, 363, 368, Apr. 2014, [Peer-reviewed], ［Internationally co-authored］
English, Scientific journal - Signal-Transducing Adaptor Protein-2 Controls the IgE-Mediated, Mast Cell-Mediated Anaphylactic Responses
Yuichi Sekine; Keigo Nishida; Satoru Yamasaki; Ryuta Muromoto; Shigeyuki Kon; Jun-ichi Kashiwakura; Kodai Saitoh; Sumihito Togi; Akihiko Yoshimura; Kenji Oritani; Tadashi Matsuda
JOURNAL OF IMMUNOLOGY, 192, 8, 3488, 3495, Apr. 2014, [Peer-reviewed]
English, Scientific journal - Jun Activation Domain-binding Protein 1 (JAB1) Is Required for the Optimal Response to Interferons
Ryuta Muromoto; Maiko Nakajima; Koki Hirashima; Toru Hirao; Shigeyuki Kon; Kazuya Shimoda; Kenji Oritani; Tadashi Matsuda
JOURNAL OF BIOLOGICAL CHEMISTRY, 288, 43, 30969, 30979, Oct. 2013, [Peer-reviewed]
English, Scientific journal - Y14 Positively Regulates TNF-alpha-Induced NF-kappa B Transcriptional Activity via Interacting RIP1 and TRADD Beyond an Exon Junction Complex Protein
Sumihito Togi; Kaname Shiga; Ryuta Muromoto; Masaya Kato; Yuki Souma; Yuichi Sekine; Shigeyuki Kon; Kenji Oritani; Tadashi Matsuda
JOURNAL OF IMMUNOLOGY, 191, 3, 1436, 1444, Aug. 2013, [Peer-reviewed]
English, Scientific journal - Frontiers in Researches of Immune Regulators
Keigo Nishida; Tadashi Matsuda
YAKUGAKU ZASSHI-JOURNAL OF THE PHARMACEUTICAL SOCIETY OF JAPAN, 133, 4, 411, 412, Apr. 2013, [Peer-reviewed]
Japanese - [Moleculary targeted therapy for JAK/STAT signaling].
Matsuda T; Kon S; Muromoto R
Nihon rinsho. Japanese journal of clinical medicine, 70 Suppl 8, 45, 51, Nov. 2012, [Peer-reviewed] - TET2 is essential for survival and hematopoietic stem cell homeostasis
K. Shide; T. Kameda; H. Shimoda; T. Yamaji; H. Abe; A. Kamiunten; M. Sekine; T. Hidaka; K. Katayose; Y. Kubuki; S. Yamamoto; T. Miike; H. Iwakiri; S. Hasuike; K. Nagata; K. Marutsuka; A. Iwama; T. Matsuda; A. Kitanaka; K. Shimoda
Leukemia, 26, 10, 2216, 2223, Oct. 2012, [Peer-reviewed], ［Internationally co-authored］
English, Scientific journal - STAP-2 interacts with and modulates BCR-ABL-mediated tumorigenesis.
Sekine Y; Ikeda O; Mizushima A; Ueno Y; Muromoto R; Yoshimura A; Kanakura Y; Oritani K; Matsuda T
Oncogene, 31, 4384, 4396, 40, Oct. 2012, [Peer-reviewed] - Roles of Cell Signaling Pathways in Cell-to-Cell Contact-Mediated Epstein-Barr Virus Transmission
Asuka Nanbo; Haruna Terada; Kunihiro Kachi; Kenzo Takada; Tadashi Matsuda
JOURNAL OF VIROLOGY, 86, 17, 9285, 9296, Sep. 2012, [Peer-reviewed]
English, Scientific journal - Signal-Transducing Adaptor Protein-2 Modulates Fas-Mediated T Cell Apoptosis by Interacting with Caspase-8
Yuichi Sekine; Chikako Yamamoto; Michinori Kakisaka; Ryuta Muromoto; Shigeyuki Kon; Dai Ashitomi; Natsuko Fujita; Akihiko Yoshimura; Kenji Oritani; Tadashi Matsuda
JOURNAL OF IMMUNOLOGY, 188, 12, 6194, 6204, Jun. 2012, [Peer-reviewed]
English, Scientific journal - Inhibitory effects of azole-type fungicides on interleukin-17 gene expression via retinoic acid receptor-related orphan receptors alpha and gamma
Hiroyuki Kojima; Ryuta Muromoto; Miki Takahashi; Shinji Takeuchi; Yukimasa Takeda; Anton M. Jetten; Tadashi Matsuda
TOXICOLOGY AND APPLIED PHARMACOLOGY, 259, 3, 338, 345, Mar. 2012, [Peer-reviewed]
English, Scientific journal - PDLIM2 inhibits T helper 17 cell development and granulomatous inflammation through degradation of STAT3
Takashi Tanaka; Yu Yamamoto; Ryuta Muromoto; Osamu Ikeda; Yuichi Sekine; Michael J. Grusby; Tsuneyasu Kaisho; Tadashi Matsuda
Science Signaling, 4, 202, ra85, 202, 06 Dec. 2011, [Peer-reviewed]
Scientific journal - PDLIM2 Inhibits T Helper 17 Cell Development and Granulomatous Inflammation Through Degradation of STAT3
Takashi Tanaka; Yu Yamamoto; Ryuta Muromoto; Osamu Ikeda; Yuichi Sekine; Michael J. Grusby; Tsuneyasu Kaisho; Tadashi Matsuda
SCIENCE SIGNALING, 4, 202, Dec. 2011, [Peer-reviewed]
English, Scientific journal - Tyk2 deficiency protects joints against destruction in anti-type II collagen antibody-induced arthritis in mice
Masayuki Ishizaki; Ryuta Muromoto; Toshihiko Akimoto; Yuya Ohshiro; Miki Takahashi; Yuichi Sekine; Hiroaki Maeda; Kazuya Shimoda; Kenji Oritani; Tadashi Matsuda
INTERNATIONAL IMMUNOLOGY, 23, 9, 575, 582, Sep. 2011, [Peer-reviewed]
English, Scientific journal - Kruppel-Associated Box-Associated Protein 1 Negatively Regulates TNF-alpha-Induced NF-kappa B Transcriptional Activity by Influencing the Interactions among STAT3, p300, and NF-kappa B/p65
Shinya Kamitani; Sumihito Togi; Osamu Ikeda; Misa Nakasuji; Asuka Sakauchi; Yuichi Sekine; Ryuta Muromoto; Kenji Oritani; Tadashi Matsuda
JOURNAL OF IMMUNOLOGY, 187, 5, 2476, 2483, Sep. 2011, [Peer-reviewed]
English, Scientific journal - Involvement of Tyrosine Kinase-2 in Both the IL-12/Th1 and IL-23/Th17 Axes In Vivo
Masayuki Ishizaki; Toshihiko Akimoto; Ryuta Muromoto; Mika Yokoyama; Yuya Ohshiro; Yuichi Sekine; Hiroaki Maeda; Kazuya Shimoda; Kenji Oritani; Tadashi Matsuda
JOURNAL OF IMMUNOLOGY, 187, 1, 181, 189, Jul. 2011, [Peer-reviewed]
English, Scientific journal - Zipper-interacting Protein Kinase (ZIPK) Modulates Canonical Wnt/beta-Catenin Signaling through Interaction with Nemo-like Kinase and T-cell Factor 4 (NLK/TCF4)
Sumihito Togi; Osamu Ikeda; Shinya Kamitani; Misa Nakasuji; Yuichi Sekine; Ryuta Muromoto; Asuka Nanbo; Kenji Oritani; Taro Kawai; Shizuo Akira; Tadashi Matsuda
JOURNAL OF BIOLOGICAL CHEMISTRY, 286, 21, 19170, 19177, May 2011, [Peer-reviewed]
English, Scientific journal - Noncanonical K27-Linked Polyubiquitination of TIEG1 Regulates Foxp3 Expression and Tumor Growth
Dong-Jun Peng; Minghui Zeng; Ryuta Muromoto; Tadashi Matsuda; Kazuya Shimoda; Malayannan Subramaniam; Thomas C. Spelsberg; Wei-Zen Wei; K. Venuprasad
JOURNAL OF IMMUNOLOGY, 186, 10, 5638, 5647, May 2011, [Peer-reviewed]
English, Scientific journal - Involvement of STAP-2 in Brk-mediated phosphorylation and activation of STAT5 in breast cancer cells
Osamu Ikeda; Akihiro Mizushima; Yuichi Sekine; Chikako Yamamoto; Ryuta Muromoto; Asuka Nanbo; Kenji Oritani; Akihiko Yoshimura; Tadashi Matsuda
CANCER SCIENCE, 102, 4, 756, 761, Apr. 2011, [Peer-reviewed]
English, Scientific journal - Interactions of STAP-2 with Brk and STAT3 Participate in Cell Growth of Human Breast Cancer Cells
Osamu Ikeda; Yuichi Sekine; Akihiro Mizushima; Misa Nakasuji; Yuto Miyasaka; Chikako Yamamoto; Ryuta Muromoto; Asuka Nanbo; Kenji Oritani; Akihiko Yoshimura; Tadashi Matsuda
JOURNAL OF BIOLOGICAL CHEMISTRY, 285, 49, 38093, 38103, Dec. 2010, [Peer-reviewed]
English, Scientific journal - Functional involvement of Daxx in gp130-mediated cell growth and survival in BaF3 cells
Ryuta Muromoto; Makoto Kuroda; Sumihito Togi; Yuichi Sekine; Asuka Nanbo; Kazuya Shimoda; Kenji Oritani; Tadashi Matsuda
EUROPEAN JOURNAL OF IMMUNOLOGY, 40, 12, 3570, 3580, Dec. 2010, [Peer-reviewed]
English, Scientific journal - BS69 cooperates with TRAF3 in the regulation of Epstein-Barr virus-derived LMP1/CTAR1-induced NF-kappa B activation
Osamu Ikeda; Yuto Miyasaka; Ryuji Yoshida; Akihiro Mizushima; Kenji Oritani; Yuichi Sekine; Makoto Kuroda; Teruhito Yasui; Masahiro Fujimuro; Ryuta Muromoto; Asuka Nanbo; Tadashi Matsuda
FEBS LETTERS, 584, 5, 865, 872, Mar. 2010, [Peer-reviewed]
English, Scientific journal - Signal-Transducing Adaptor Protein-2 Regulates Stromal Cell-Derived Factor-1 alpha-Induced Chemotaxis in T Cells
Yuichi Sekine; Osamu Ikeda; Satoshi Tsuji; Chikako Yamamoto; Ryuta Muromoto; Asuka Nanbo; Kenji Oritani; Akihiko Yoshimura; Tadashi Matsuda
JOURNAL OF IMMUNOLOGY, 183, 12, 7966, 7974, Dec. 2009, [Peer-reviewed]
English, Scientific journal - A single polymorphic amino acid on Toxoplasma gondii kinase ROP16 determines the direct and strain-specific activation of Stat3
Masahiro Yamamoto; Daron M. Standley; Seiji Takashima; Hiroyuki Saiga; Megumi Okuyama; Hisako Kayama; Emi Kubo; Hiroshi Ito; Mutsumi Takaura; Tadashi Matsuda; Dominique Soldati-Favre; Kiyoshi Takeda
JOURNAL OF EXPERIMENTAL MEDICINE, 206, 12, 2747, 2760, Nov. 2009, [Peer-reviewed], ［Internationally co-authored］
English, Scientific journal - Silencing Mediator of Retinoic Acid and Thyroid Hormone Receptor Regulates Enhanced Activation of Signal Transducer and Activator of Transcription 3 by Epstein-Barr Virus-Derived Epstein-Barr Nuclear Antigen 2
Osamu Ikeda; Sumihito Togi; Shinya Kamitani; Ryuta Muromoto; Yuichi Sekine; Asuka Nanbo; Masahiro Fujimuro; Tadashi Matsuda
BIOLOGICAL & PHARMACEUTICAL BULLETIN, 32, 7, 1283, 1285, Jul. 2009, [Peer-reviewed]
English, Scientific journal - STAP-2 is phosphorylated at tyrosine-250 by Brk and modulates Brk-mediated STAT3 activation
Osamu Ikeda; Yuto Miyasaka; Yuichi Sekine; Akihiro Mizushima; Ryuta Muromoto; Asuka Nanbo; Akihiko Yoshimura; Tadashi Matsuda
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 384, 1, 71, 75, Jun. 2009, [Peer-reviewed]
English, Scientific journal - The protein content of an adaptor protein, STAP-2 is controlled by E3 ubiquitin ligase Cbl
Yuichi Sekine; Chikako Yamamoto; Osamu Ikeda; Ryuta Muromoto; Asuka Nanbo; Kenji Oritani; Akihiko Yoshimura; Tadashi Matsuda
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 384, 2, 187, 192, Jun. 2009, [Peer-reviewed]
English, Scientific journal - BS69 negatively regulates the canonical NF-kappa B activation induced by Epstein-Barr virus-derived LMP1
Osamu Ikeda; Yuichi Sekine; Akihiro Mizushima; Kenji Oritani; Teruhito Yasui; Masahiro Fujimuro; Ryuta Muromoto; Asuka Nanbo; Tadashi Matsuda
FEBS LETTERS, 583, 10, 1567, 1574, May 2009, [Peer-reviewed]
English, Scientific journal - The exon-junction complex proteins, Y14 and MAGOH regulate STAT3 activation
Ryuta Muromoto; Naohisa Taira; Osamu Ikeda; Kaname Shiga; Shinya Kamitani; Sumihito Togi; Shiho Kawakami; Yuichi Sekine; Asuka Nanbo; Kenji Oritani; Tadashi Matsuda
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 382, 1, 63, 68, Apr. 2009, [Peer-reviewed]
English, Scientific journal - HDAC3 influences phosphorylation of STAT3 at serine 727 by interacting with PP2A
Sumihito Togi; Shinya Kamitani; Shiho Kawakami; Osarnu Ikeda; Ryuta Muromoto; Asuka Nanbo; Tadashi Matsuda
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 379, 2, 616, 620, Feb. 2009, [Peer-reviewed]
English, Scientific journal - Epstein-Barr virus-derived EBNA2 regulates STAT3 activation
Ryuta Murornoto; Osamu Ikeda; Kanako Okabe; Sumihito Togi; Shinya Kamitani; Masahiro Fujimuro; Shizuko Harada; Kenji Oritani; Tadashi Matsud
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 378, 3, 439, 443, Jan. 2009, [Peer-reviewed]
English, Scientific journal - Comparative study on the nuclear hormone receptor activity of various phytochemicals and their metabolites by reporter gene assays using Chinese hamster ovary cells.
Takeuchi S; Takahashi T; Sawada Y; Iida M; Matsuda T; Kojima H
Biol. Pharm. Bull., 32, 2, 195, 202, 2009, [Peer-reviewed] - In vitro screening for aryl hydrocarbon receptor agonistic activity in 200 pesticides using a highly sensitive reporter cell line, DR-EcoScreen cells, and in vivo mouse liver cytochrome P450-1A induction by propanil, diuron and linuron
Shinji Takeuchi; Mitsuru Iida; Hisatoshi Yabushita; Tadashi Matsuda; Hiroyuki Kojima
CHEMOSPHERE, 74, 1, 155, 165, Dec. 2008, [Peer-reviewed]
English, Scientific journal - Enhanced c-Fms/M-CSF receptor signaling and wound-healing process in bone marrow-derived macrophages of signal-transducing adaptor protein-2 (STAP-2) deficient mice
Osamu Ikeda; Yuichi Sekine; Ryuta Muromoto; Norihiko Ohbayashi; Akihiko Yoshimura; Tadashi Matsuda
BIOLOGICAL & PHARMACEUTICAL BULLETIN, 31, 9, 1790, 1793, Sep. 2008, [Peer-reviewed]
English, Scientific journal - An RNA biding protein, Y14 interacts with and modulates STAT3 activation
Norihiko Ohbayashi; Naohisa Taira; Shiho Kawakami; Sumihito Togi; Noriko Sato; Osamu Ikeda; Shinya Kamitani; Ryuta Muromoto; Yuichi Sekine; Tadashi Matsuda
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 372, 3, 475, 479, Aug. 2008, [Peer-reviewed]
English, Scientific journal - Physical and functional interactions between ZIP kinase and UbcH5
Norihiko Ohbayashi; Katsuya Okada; Shiho Kawakami; Sumihito Togi; Noriko Sato; Osamu Ikeda; Shinya Kamitani; Ryuta Muromoto; Yuichi Sekine; Taro Kawai; Shizuo Akira; Tadashi Matsuda
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 372, 4, 708, 712, Aug. 2008, [Peer-reviewed]
English, Scientific journal - STAP-2 negatively regulates both canonical and noncanonical NF-kappa B activation induced by Epstein-Barr virus-derived latent membrane protein 1
Osamu Ikeda; Yuichi Sekine; Teruhito Yasui; Kenji Oritani; Kenji Sugiyma; Ryuta Muromoto; Norihiko Ohbayashi; Akihiko Yoshimura; Tadashi Matsuda
MOLECULAR AND CELLULAR BIOLOGY, 28, 16, 5027, 5042, Aug. 2008, [Peer-reviewed]
English, Scientific journal - The IL-6 family of cytokines modulates STAT3 activation by desumoylation of PML through SENP1 induction
Norihiko Ohbayashi; Shiho Kawakami; Ryuta Muromoto; Sumihito Togi; Osamu Ikeda; Shinya Kamitani; Yuichi Sekine; Tsutomu Honjoh; Tadashi Matsuda
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 371, 4, 823, 828, Jul. 2008, [Peer-reviewed]
English, Scientific journal - KAP1 regulates type I interferon/STAT1-mediated IRF-1 gene expression
Shinya Kamitani; Norihiko Ohbayashi; Osamu Ikeda; Sumihito Togi; Ryuta Muromoto; Yuichi Sekine; Kazuhide Ohta; Hironobu Ishiyama; Tadashi Matsuda
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 370, 2, 366, 370, May 2008, [Peer-reviewed]
English, Scientific journal - Sumoylation of Smad3 stimulates its nuclear export during PIASy-mediated suppression of TGF-beta signaling
Seiyu Imoto; Norihiko Ohbayashi; Osamu Ikeda; Shinya Kamitani; Ryuta Muromoto; Yuichi Sekine; Tadashi Matsuda
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 370, 2, 359, 365, May 2008, [Peer-reviewed]
English, Scientific journal - Physical and functional interactions between STAT3 and KAP1.
Tsuruma R; Ohbayashi N; Kamitani S; Ikeda O; Sato N; Muromoto R; Sekine Y; Oritani K; Matsuda T
Oncogene, 27, 3054, 3059, 21, May 2008, [Peer-reviewed] - BART is essential for nuclear retention of STAT3
Ryuta Muromoto; Yuichi Sekine; Seiyu Imoto; Osamu Ikeda; Taichiro Okayama; Noriko Sato; Tadashi Matsuda
INTERNATIONAL IMMUNOLOGY, 20, 3, 395, 403, Mar. 2008, [Peer-reviewed]
English, Scientific journal - LIF- and IL-6-Induced acetylation of STAT3 at Lys-685 through PI3K/Akt activation
Norihiko Ohbayashi; Osamu Ikeda; Naohisa Taira; Yu Yamamoto; Ryuta Muromoto; Yalchi Sekine; Kenji Sugiyama; Tsutomu Honjoh; Tadashi Matsuda
BIOLOGICAL & PHARMACEUTICAL BULLETIN, 30, 10, 1860, 1864, Oct. 2007, [Peer-reviewed]
English, Scientific journal - Chronic thrombopoietin overexpression induces mesangioproliferative glomerulopathy in mice
Haruko K. Shimoda; Masahiro Yamamoto; Kotaro Shide; Kenjirou Kamezaki; Tadashi Matsuda; Katsuhiro Ogawa; Mine Harada; Kazuya Shimoda
AMERICAN JOURNAL OF HEMATOLOGY, 82, 9, 802, 806, Sep. 2007, [Peer-reviewed]
English, Scientific journal - Tyk2 mutation homologous to V617F Jak2 is not found in essential thrombocythaemia, although it induces constitutive signaling and growth factor independence
Kotaro Shide; Kazuya Shimoda; Kenjirou Kamezaki; Haruko Kakumitsu; Takashi Kumano; Akihiko Numata; Fumihiko Ishikawa; Katsuto Takenaka; Ken Yamamoto; Tadashi Matsuda; Mine Harada
LEUKEMIA RESEARCH, 31, 8, 1077, 1084, Aug. 2007, [Peer-reviewed]
English, Scientific journal - Signal-transducing adaptor protein-2 regulates integrin-mediated T cell adhesion through protein degradation of focal adhesion kinase
Yuichi Sekine; Satoshi Tsuji; Osamu Ikeda; Kenji Sugiyma; Kenji Oritani; Kazuya Shimoda; Ryuta Muromoto; Norihiko Ohbayashi; Akihiko Yoshimura; Tadashi Matsuda
JOURNAL OF IMMUNOLOGY, 179, 4, 2397, 2407, Aug. 2007, [Peer-reviewed]
English, Scientific journal - STAP-2 regulates c-Fms/M-CSF receptor signaling in murine macrophage Raw 264.7 cells
Osamu Ikeda; Yuichi Sekine; Michinori Kakisaka; Satoshi Tsuji; Ryuta Muromoto; Norihiko Ohbayashi; Kenji Oritani; Akhko Yoshimura; Tadashi Matsuda
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 358, 3, 931, 937, Jul. 2007, [Peer-reviewed]
English, Scientific journal - Leukemia inhibitory factor-induced phosphorylation of STAP-2 on tyrosine-250 is involved in its STAT3-enhancing activity
Yuichi Sekine; Satoshi Tsuji; Osamu Ikeda; Michinori Kakisaka; Kenji Sugiyama; Akihiko Yoshimura; Tadashi Matsuda
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 356, 2, 517, 522, May 2007, [Peer-reviewed]
English, Scientific journal - DUSP22/LMW-DSP2 regulates estrogen receptor-α-mediated signaling through dephosphorylation of Ser-118
Sekine, Y.; Ikeda, O.; Hayakawa, Y.; Tsuji, S.; Imoto, S.; Aoki, N.; Sugiyama, K.; Matsuda, T.
Oncogene, 26, 41, 6038, 6049, 2007, [Peer-reviewed]
Scientific journal - In vitro screening of 200 pesticides for agonistic activity via mouse peroxisome proliferator-activated receptor (PPAR)alpha and PPAR gamma and quantitative analysis of in vivo induction pathway
Shinji Takeuchi; Tadashi Matsuda; Satoshi Kobayashi; Tetsuo Takahashi; Hiroyuki Kojima
TOXICOLOGY AND APPLIED PHARMACOLOGY, 217, 3, 235, 244, Dec. 2006, [Peer-reviewed]
English, Scientific journal - Receptor specific downregulation of cytokine signaling by autophosphorylation in the FERM domain of Jak2
Megumi Funakoshi-Tago; Stephane Pelletier; Tadashi Matsuda; Evan Parganas; James N. Ihle
EMBO JOURNAL, 25, 20, 4763, 4772, Oct. 2006, [Peer-reviewed], ［Internationally co-authored］
English, Scientific journal - Sumoylation of Daxx regulates IFN-induced growth suppression of B lymphocytes and the hormone receptor-mediated transactivation
Ryuta Muromoto; Masato Ishida; Kenji Sugiyama; Yuichi Sekine; Kenji Oritani; Kazuya Shimoda; Tadashi Matsuda
JOURNAL OF IMMUNOLOGY, 177, 2, 1160, 1170, Jul. 2006, [Peer-reviewed]
English, Scientific journal - Phosphorylation of threonine-265 in Zipper-interacting protein kinase plays an important role in its activity and is induced by IL-6 family cytokines
N Sato; N Kamada; R Muromoto; T Kawai; K Sugiyama; T Watanabe; S Imoto; Y Sekine; N Ohbayashi; M Ishida; S Akira; T Matsuda
IMMUNOLOGY LETTERS, 103, 2, 127, 134, Mar. 2006, [Peer-reviewed]
English, Scientific journal - Physical and functional interactions between Daxx and STAT3.
Muromoto R; Nakao K; Watanabe T; Sato N; Sekine Y; Sugiyama K; Oritani K; Shimoda K; Matsuda T
Oncogene, 25, 14, 2131, 2136, Nature Publishing Group, Mar. 2006, [Peer-reviewed]
English, Signal transducer and activator of transcription 3 (STAT3) play key roles in the intracellular signaling pathways of the interleukin (IL)-6 family of cytokines, which exhibit a diverse set of cellular responses, including cell proliferation and differentiation. Dysregulated IL-6/STAT3 signaling is involved in the pathogenesis of several diseases, for example autoimmune diseases and tumors. Type I interferon (IFN) induces the expression of proapoptotic genes and has been used in the clinical treatment of several tumors. In the present study, we found that type I IFN suppressed IL-6/STAT3-mediated transcription and gene expression. Furthermore, a type I IFN-induced protein, Daxx, also suppressed STAT3-mediated transcriptional activation, while overexpression of Daxx inhibited IL-6/STAT3-mediated gene expression. Importantly, small-interfering RNA-mediated reduction of Daxx expression enhanced IL-6/leukemia inhibitory factor (LIF)-induced STAT3-dependent transcription. Co-immunoprecipitation studies revealed a physical interaction between Daxx and STAT3 in transiently transfected 293T cells. We further found that Daxx and STAT3 were co-localized in the nucleus. These results indicate that Daxx may serve as a transcriptional regulator of type I IFN-mediated suppression of the IL-6/STAT3 signaling pathway. - Physical and functional interactions between STAT3 and Kaposi's sarcoma-associated herpesvirus-encoded LANA
R Muromoto; K Okabe; M Fujimuro; K Sugiyama; H Yokosawa; T Seya; T Matsuda
FEBS LETTERS, 580, 1, 93, 98, Jan. 2006, [Peer-reviewed]
English, Scientific journal - Modulation of TLR4 signaling by a novel adaptor protein signal-transducing adaptor protein-2 in macrophages
Y Sekine; T Yumioka; T Yamamoto; R Muromoto; S Imoto; K Sugiyma; K Oritani; K Shimoda; M Minoguchi; S Akira; A Yoshimura; T Matsuda
JOURNAL OF IMMUNOLOGY, 176, 1, 380, 389, Jan. 2006, [Peer-reviewed]
English, Scientific journal - Regulation of STAT3-mediated signaling by LMW-DSP2
Sekine, Y.; Tsuji, S.; Ikeda, O.; Sato, N.; Aoki, N.; Aoyama, K.; Sugiyama, K.; Matsuda, T.
Oncogene, 25, 42, 5801, 5806, 2006, [Peer-reviewed]
Scientific journal - Physical and functional interactions between STAT3 and ZIP kinase
N Sato; T Kawai; K Sugiyama; R Muromoto; S Imoto; Y Sekine; M Ishida; S Akira; T Matsuda
INTERNATIONAL IMMUNOLOGY, 17, 12, 1543, 1552, Dec. 2005, [Peer-reviewed]
English, Scientific journal - Nuclear retention of STAT3 through the coiled-coil domain regulates its activity
N Sato; R Tsuruma; S Imoto; Y Sekine; R Muromoto; K Sugiyama; T Matsuda
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 336, 2, 617, 624, Oct. 2005, [Peer-reviewed]
English, Scientific journal - A novel mutation in the juxtamembrane intracellular sequence of the granulocyte colony-stimulating factor (G-CSF) receptor gene in a patient with severe congenital neutropenia augments G-CSF proliferation activity but not through the MAP kinase cascade
T Yokoyama; S Okamura; Y Asano; K Kamezaki; A Numata; H Kakumitsu; K Shide; H Nakashima; T Kanaji; Y Sekine; Y Mizuno; J Okamura; T Matsuda; M Harada; Y Niho; K Shimoda
INTERNATIONAL JOURNAL OF HEMATOLOGY, 82, 1, 28, 34, Jul. 2005, [Peer-reviewed]
English, Scientific journal - Novel pathway for LPS-induced afferent vagus nerve activation: Possible role of nodose ganglion
Hosoi, T; Okuma, Y; Matsuda, T; Nomura, Y
AUTONOMIC NEUROSCIENCE-BASIC & CLINICAL, 120, 1-2, 104, 107, ELSEVIER SCIENCE BV, 15 Jun. 2005, [Peer-reviewed]
Scientific journal, The afferent vagus nerve has been suggested to be an important component for transmitting peripheral immune signals to the brain. However, there is inconsistent evidence showing that subdiaphragmatic vagotomy did not inhibit the brain mediated behavioral and neural effects induced by the peripheral application of lipopolysaccharide (LPS). LPS triggers innate immune cells through Toll-like receptor 4 (TLR4). In the present study, we found that TLR4 mRNA and protein was expressed in the rat nodose ganglion. Thus, it is suggested that LPS could activate afferent vagus nerve at the level of nodose ganglion, which exists centrally from the subdiaphragmatic level of vagus nerve. The results could provide evidence for the novel pathway of LPS-induced afferent vagus nerve activation. (c) 2005 Elsevier B.V. All rights reserved. - Differential effects of phthalate esters on transcriptional activities via human estrogen receptors alpha and beta, and androgen receptor
S Takeuchi; M Iida; S Kobayashi; K Jin; T Matsuda; H Kojima
TOXICOLOGY, 210, 2-3, 223, 233, Jun. 2005, [Peer-reviewed]
English, Scientific journal - Vasoactive intestinal peptide and pituitary adenylate cyclase activating polypeptide stimulate interleukin-6 production in prostate cancer cells and prostatic epithelial cells.
Nagakawa O; Junicho A; Akashi T; Koizumi K; Matsuda T; Fuse H; Saiki I
Oncology reports, 13, 6, 1217, 1221, Jun. 2005, [Peer-reviewed] - Roles for lysine residues of the MH2 domain of Smad3 in transforming growth factor-beta e signaling
S Imoto; K Sugiyama; Y Sekine; T Matsuda
FEBS LETTERS, 579, 13, 2853, 2862, May 2005, [Peer-reviewed]
English, Scientific journal - Physical and functional interactions between STAP-2/BKS and STAT5
Y Sekine; T Yamamoto; T Yumioka; K Sugiyama; S Tsuji; K Oritani; K Shimoda; M Minoguchi; A Yoshimura; T Matsuda
JOURNAL OF BIOLOGICAL CHEMISTRY, 280, 9, 8188, 8196, Mar. 2005, [Peer-reviewed]
English, Scientific journal - Roles of Stat3 and ERK in G-CSF signaling
K Kamezaki; K Shimoda; A Numata; T Haro; H Kakumitsu; M Yoshie; Y Yamamoto; K Takeda; T Matsuda; M Akira; K Ogawa; O Harada
STEM CELLS, 23, 2, 252, 263, Feb. 2005, [Peer-reviewed]
English, Scientific journal - Cytokine induction by a bacterial DNA-specific modified base
H Tsuchiya; T Matsuda; H Harashima; H Kamiya
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 326, 4, 777, 781, Jan. 2005, [Peer-reviewed]
English, Scientific journal - Determination of the transphosphorylation sites of Jak2 kinase
T Matsuda; J Feng; BA Witthuhn; Y Sekine; JN Ihle
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 325, 2, 586, 594, Dec. 2004, [Peer-reviewed], ［Internationally co-authored］
English, Scientific journal - Molecular dynamics of STAT3 on IL-6 signaling pathway in living cells
K Watanabe; K Saito; M Kinjo; T Matsuda; M Tamura; S Kon; T Miyazaki; T Uede
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 324, 4, 1264, 1273, Nov. 2004, [Peer-reviewed]
English, Scientific journal - Bacterial endotoxin induces IL-20 expression in the glial cells
T Hosoi; S Wada; S Suzuki; Y Okuma; S Akira; T Matsuda; Y Nomura
MOLECULAR BRAIN RESEARCH, 130, 1-2, 23, 29, Nov. 2004, [Peer-reviewed]
English, Scientific journal - Bacterial endotoxin induces STAT3 activation in the mouse brain
T Hosoi; Y Okuma; T Kawagishi; Qi, X; T Matsuda; Y Nomura
BRAIN RESEARCH, 1023, 1, 48, 53, Oct. 2004, [Peer-reviewed]
English, Scientific journal - Differential expression of integrin subunits in DU-145/AR prostate cancer cells
O Nagakawa; T Akashi; Y Hayakawa; A Junicho; K Koizumi; Y Fujiuchi; Y Furuya; T Matsuda; H Fuse; Saiki, I
ONCOLOGY REPORTS, 12, 4, 837, 841, Oct. 2004, [Peer-reviewed]
English, Scientific journal - Hapten-induced contact hypersensitivity is enhanced in Tyk2-deficient mice
M Hosogi; H Tonogaito; A Aioi; K Hamada; K Shimoda; R Muromoto; T Matsuda; Y Miyachi
JOURNAL OF DERMATOLOGICAL SCIENCE, 36, 1, 51, 56, Oct. 2004, [Peer-reviewed]
English, Scientific journal - The role of Tyk2, Stat1 and Stat4 in LPS-induced endotoxin signals
K Kamezaki; K Shimoda; A Numata; T Matsuda; K Nakayama; M Harada
INTERNATIONAL IMMUNOLOGY, 16, 8, 1173, 1179, Aug. 2004, [Peer-reviewed]
English, Scientific journal - Tyrosine kinase 2 interacts with and phosphorylates receptor for-activated c kinase-1, a WD motif-containing protein
T Haro; K Shimoda; H Kakumitsu; K Kamezaki; A Numata; F Ishikawa; Y Sekine; R Muromoto; T Matsuda; M Harada
JOURNAL OF IMMUNOLOGY, 173, 2, 1151, 1157, Jul. 2004, [Peer-reviewed]
English, Scientific journal - The RING domain of PIASy is involved in the suppression of bone morphogenetic protein-signaling pathway
S Imoto; K Sugiyama; T Yamamoto; T Matsuda
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 319, 1, 275, 282, Jun. 2004, [Peer-reviewed]
English, Scientific journal - Physical and functional interactions between Daxx and TSG101
R Muromoto; K Sugiyama; T Yamamoto; K Oritani; K Shimoda; T Matsuda
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 316, 3, 827, 833, Apr. 2004, [Peer-reviewed]
English, Scientific journal - Cross-talk between endocrine-disrupting chemicals and cytokine signaling through estrogen receptors
Y Sekine; T Yamamoto; T Yumioka; S Imoto; H Kojima; T Matsuda
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 315, 3, 692, 698, Mar. 2004, [Peer-reviewed]
English, Scientific journal - Physical and functional interactions between Daxx and DNA methyltransferase 1-associated protein, DMAP1
R Muromoto; K Sugiyama; A Takachi; S Imoto; N Sato; T Yamamoto; K Oritani; K Shimoda; T Matsuda
JOURNAL OF IMMUNOLOGY, 172, 5, 2985, 2993, Mar. 2004, [Peer-reviewed]
English, Scientific journal - Involvement of NF-kappa B in TGF-beta-mediated suppression of IL-4 signaling
T Yamamoto; S Imoto; Y Sekine; K Sugiyama; T Akimoto; A Muraguchi; T Matsuda
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 313, 3, 627, 634, Jan. 2004, [Peer-reviewed]
English, Scientific journal - Regulation of TGF-beta signaling by PIASy
S Imoto; K Sugiyama; T Yamamoto; T Matsuda
IMMUNOLOGY 2004: CYTOKINE NETWORK, REGULATORY CELLS, SIGNALING, AND APOPTOSIS, 253, 256, 2004, [Peer-reviewed]
English, International conference proceedings - Limitin, an interferon-like cytokine, transduces inhibitory signals on B-cell growth through activation of Tyk2, but not Stat1, followed by induction and nuclear translocation of Daxx
K Aoki; K Shimoda; K Oritani; T Matsuda; K Kamezaki; R Muromoto; A Numata; S Tamiya; T Haro; F Ishikawa; K Takase; T Yamamoto; T Yumioka; T Miyamoto; K Nagafuji; H Gondo; S Nagafuchi; K Nakayama; M Harada
EXPERIMENTAL HEMATOLOGY, 31, 12, 1317, 1322, Dec. 2003, [Peer-reviewed]
English, Scientific journal - Intracellular signal transduction of interferon on the suppression of haematopoietic progenitor cell growth
K Kato; K Kamezaki; K Shimoda; A Numata; T Haro; K Aoki; F Ishikawa; K Takase; H Ariyama; T Matsuda; T Miyamoto; K Nagafuji; H Gondo; KI Nakayama; M Harada
BRITISH JOURNAL OF HAEMATOLOGY, 123, 3, 528, 535, Nov. 2003, [Peer-reviewed]
English, Scientific journal - Regulation of transforming growth factor-beta signaling by protein inhibitor of activated STAT, PIASy through Smad3
S Imoto; K Sugiyama; R Muromoto; N Sato; T Yamamoto; T Matsuda
JOURNAL OF BIOLOGICAL CHEMISTRY, 278, 36, 34253, 34258, Sep. 2003, [Peer-reviewed]
English, Scientific journal - Regulation of Fc epsilon RI-mediated signaling by an adaptor protein STAP-2/BSK in rat basophilic leukemia RBL-2H3 cells
T Yamamoto; T Yumioka; Y Sekine; N Sato; M Minoguchi; A Yoshimura; T Matsuda
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 306, 3, 767, 773, Jul. 2003, [Peer-reviewed]
English, Scientific journal - Molecular interactions between STAT3 and protein inhibitor of activated STAT3, and androgen receptor
T Yamamoto; N Sato; Y Sekine; T Yumioka; S Imoto; A Junicho; H Fuse; T Matsuda
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 306, 2, 610, 615, Jun. 2003, [Peer-reviewed]
English, Scientific journal - Daxx enhances Fas-mediated apoptosis in a murine pro-B cell line, BAF3
R Muromoto; T Yamamoto; T Yumioka; Y Sekine; K Sugiyama; K Shimoda; K Oritani; T Matsuda
FEBS LETTERS, 540, 1-3, 223, 228, Apr. 2003, [Peer-reviewed]
English, Scientific journal - STAP-2/BKS, an adaptor/docking protein, modulates STAT3 activation in acute-phase response through its YXXQ motif
M Minoguchi; S Minoguchi; D Aki; A Joo; T Yamamoto; T Yumioka; T Matsuda; A Yoshimura
JOURNAL OF BIOLOGICAL CHEMISTRY, 278, 13, 11182, 11189, Mar. 2003, [Peer-reviewed]
English, Scientific journal - Involvement of heat-shock protein 90 in the interleukin-6-mediated signaling pathway through STAT3
N Sato; T Yamamoto; Y Sekine; T Yumioka; A Junicho; H Fuse; T Matsuda
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 300, 4, 847, 852, Jan. 2003, [Peer-reviewed]
English, Scientific journal - Cutting edge: Tyk2 is required for the induction and nuclear translocation of Daxx which regulates IFN-alpha-induced suppression of B lymphocyte formation
K Shimoda; K Kamesaki; A Numata; K Aoki; T Matsuda; K Oritani; S Tamiya; K Kato; K Takase; R Imamura; T Yamamoto; T Miyamoto; K Nagafuji; H Gondo; S Nagafuchi; KI Nakayama; M Harada
JOURNAL OF IMMUNOLOGY, 169, 9, 4707, 4711, Nov. 2002, [Peer-reviewed]
English, Scientific journal - Mapping of the sites responsible for factor I-cofactor activity for cleavage of C3b and C4b on human C4b-binding protein (C4bp) by deletion mutagenesis
A Fukui; T Yuasa-Nakagawa; Y Murakami; K Funami; N Kishi; T Matsuda; T Fujita; T Seya; S Nagasawa
JOURNAL OF BIOCHEMISTRY, 132, 5, 719, 728, Nov. 2002, [Peer-reviewed]
English, Scientific journal - Lymphoid enhancer-binding factor-1 binds and activates the recombination-activating gene-2 promoter together with c-Myb and Pax-5 in immature B cells
ZX Jin; H Kishi; XC Wei; T Matsuda; S Saito; A Muraguchi
JOURNAL OF IMMUNOLOGY, 169, 7, 3783, 3792, Oct. 2002, [Peer-reviewed]
English, Scientific journal - The nuclear isoform of protein-tyrosine phosphatase TC-PTP regulates interleukin-6-mediated signaling pathway through STAT3 dephosphorylation
T Yamamoto; Y Sekine; K Kashima; A Kubota; N Sato; N Aoki; T Matsuda
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 297, 4, 811, 817, Oct. 2002, [Peer-reviewed]
English, Scientific journal - Cross-talk between bone morphogenic proteins and estrogen receptor signaling
T Yamamoto; F Saatcioglu; T Matsuda
ENDOCRINOLOGY, 143, 7, 2635, 2642, Jul. 2002, [Peer-reviewed]
English, Scientific journal - Characterization of chromatin structure and enhancer elements for murine recombination activating gene-2
XC Wei; H Kishi; ZX Jin; WP Zhao; S Kondo; T Matsuda; S Saito; A Muraguchi
JOURNAL OF IMMUNOLOGY, 169, 2, 873, 881, Jul. 2002, [Peer-reviewed]
English, Scientific journal - Partial impairment of interleukin-12 (IL-12) and IL-18 signaling in Tyk2-deficient mice
K Shimoda; H Tsutsui; K Aoki; K Kato; T Matsuda; A Numata; K Takase; T Yamamoto; H Nukina; T Hoshino; Y Asano; H Gondo; T Okamura; S Okamura; KI Nakayama; K Nakanishi; Y Niho; M Harada
BLOOD, 99, 6, 2094, 2099, Mar. 2002, [Peer-reviewed]
English, Scientific journal - Vasoactive intestinal peptide (VIP) enhances the cell motility of androgen receptor-transfected DU-145 prostate cancer cells (DU-145/AR)
O Nagakawa; J Murata; A Junicho; T Matsuda; Y Fujiuchi; H Fuse; Saiki, I
CANCER LETTERS, 176, 1, 93, 99, Feb. 2002, [Peer-reviewed]
English, Scientific journal - Cooperative binding of c-Myb and Pax-5 activates the RAG-2 promoter in immature B cells
H Kishi; ZX Jin; XC Wei; T Nagata; T Matsuda; S Saito; A Muraguchi
BLOOD, 99, 2, 576, 583, Jan. 2002, [Peer-reviewed]
English, Scientific journal - Cross-talk between transforming growth factor-beta and estrogen receptor signaling through Smad3
T Matsuda; T Yamamoto; A Muraguchi; F Saatcioglu
JOURNAL OF BIOLOGICAL CHEMISTRY, 276, 46, 42908, 42914, Nov. 2001, [Peer-reviewed], ［Internationally co-authored］
English, Scientific journal - The role of interleukin 6 in plasmacytomagenesis.
T. Hirano; S. Suematsu; T. Matsusaka; T. Matsuda; T. Kishimoto
Ciba Foundation symposium, 167, 188, 196200, 1992
English, Scientific journal - INTERLEUKIN-6 (IL-6) AND ITS RECEPTOR (IL-6R) IN MYELOMA PLASMACYTOMA
S SUEMATSU; M HIBI; T SUGITA; M SAITO; M MURAKAMI; T MATSUSAKA; T MATSUDA; T HIRANO; T TAGA; T KISHIMOTO
MECHANISMS IN B-CELL NEOPLASIA 1990, 13, 22, 1990, [Peer-reviewed]
English, International conference proceedings - IL-6 BSF2 IN NORMAL AND ABNORMAL REGULATION OF IMMUNE-RESPONSES
T MATSUDA; S SUEMATSU; M KAWANO; K YOSHIZAKI; B TANG; O TANABE; T NAKAJIMA; S AKIRA; T HIRANO; T KISHIMOTO
REGULATION OF THE ACUTE PHASE AND IMMUNE RESPONSES : INTERLEUKIN-6, 557, 466, 477, 1989, [Peer-reviewed]
English, International conference proceedings - MOLECULAR-CLONING OF THE CDNAS FOR INTERLEUKIN-6 B-CELL STIMULATORY FACTOR-II AND ITS RECEPTOR
T HIRANO; T TAGA; K YAMASAKI; T MATSUDA; K YASUKAWA; Y HIRATA; H YAWATA; O TANABE; S AKIRA; T KISHIMOTO
REGULATION OF THE ACUTE PHASE AND IMMUNE RESPONSES : INTERLEUKIN-6, 557, 167, 180, 1989, [Peer-reviewed]
English, International conference proceedings - INTERLEUKIN-6 AND ITS RECEPTOR IN IMMUNE REGULATION
T KISHIMOTO; T TAGA; T MATSUDA; M HIBI; S SUEMATSU; B TANG; H YAWATA; Y HIRATA; K YAMASAKI; T HIRANO
PROGRESS IN IMMUNOLOGY, VOL 7, 633, 640, 1989, [Peer-reviewed]
English, International conference proceedings - Pathogenic significance of BSF-2/IL-6 in castleman's disease
K. Yoshizaki; T. Matsuda; N. Nishimoto; T. Kuritani; L. Taeho; K. Aozasa; T. Nakahata; H. Tagoh; T. Komori; S. Kishimoto; T. Hirano; T. Kishimoto
International Journal of Immunopharmacology, 10, 1, 13, 1988, [Peer-reviewed]
English, International conference proceedings - Abnormal production of interleukin 6 and B cell anomaly.
平野 俊夫; 松田 正; 唐 波; 田賀 哲也; 吉崎 和幸; 宮坂 信之; 河野 道生; 志水 正敏; 岸本 忠三
Jpn. J. Clin. Immunol., 11, 5, 460, 463, The Japan Society for Clinical Immunology, 1988
Japanese - B cell stimulatory factor 2(BSF2/IL-6) and rheumatoid arthritis.
HIRANO Toshio; MATSUDA Tadashi; TURNER Martin; FELDMANN Marc; TANG Bo; MIYASAKA Nobuyuki; SHIMIZU Masatoshi; KISHIMOTO Tadamitsu
Proceedings of the Japan Academy, 63, 7, 281, 283, The Japan Academy, 1987
English
- ここまで進んだJAK阻害薬の臨床 JAK/TYK2シグナルの生理学と病理学
松田正; 織谷健司, 炎症と免疫, 34, 1, 2026 - Investigation of inhibitory effect of butyrate on IL-33-induced basophil activation
柏倉淳一; 上坂瑞希; 滝田倖実歌; 宮崎達矢; 松田正, 日本薬学会年会要旨集(Web), 146th, 2026 - Investigation of the functional role of STAP-1 in basophils
吉岡優; 遠山知花; 河原生知; 松田正; 柏倉淳一, 日本薬学会年会要旨集(Web), 146th, 2026 - IL-6/STAT3 Signaling Pathways: Molecular Insights and Emerging Thereapeutic Targets
松田正, YAKUGAKU ZASSHI (Web), 145, 12, 2025 - Analysis of the relationship between protein NEDDylation mechanism and Regnase-1 activity
YU Tingchi; 小森雄喜; 室本竜太; 松田正, 日本免疫毒性学会学術年会講演要旨集, 30th, 2023 - Effect of Benzo[a]pyrene on IL-17 mediated signaling
成家康太; 室本竜太; 松田正, 衛生薬学・環境トキシコロジー講演要旨集, 2023, 2023 - Role of Tyk2 in immune and inflammatory responses
室本竜太; 松田正, 日本薬学会年会要旨集(Web), 143rd, 2023 - Neddylation inhibition inactivates Regnase-1 via MALT1-mediated cleavage
YU Tingchi; 小森雄喜; 室本竜太; 松田正, 日本薬学会年会要旨集(Web), 143rd, 2023 - Upregulated Glo1 gene expression in Tyk2-deficient macrophages
阿部丈一朗; 宮下清隆; 美濃口広弥; 室本竜太; 松田正, 日本薬学会年会要旨集(Web), 143rd, 2023 - Role of Tyk2 in LPS-induced acute lung injury model in mice
金光聡馬; 大久保優菜; 室本竜太; 松田正, 日本薬学会年会要旨集(Web), 143rd, 2023 - X線小角散乱(SEC-SAXS)による,Breast tumor kinaseの活性化機構の解明
宇賀神魁; 武井梓穂; 松田正; 尾瀬農之, 日本蛋白質科学会年会プログラム・要旨集, 23rd (CD-ROM), 2023 - アダプター蛋白質介在に伴う,乳がん特異的キナーゼの活性亢進評価
武井梓穂; 宇賀神魁; 中迫純希; 松尾友樹; 神田諒; 前仲勝実; 松田正; 姚閔; 尾瀬農之, 日本蛋白質科学会年会プログラム・要旨集, 23rd (CD-ROM), 2023 - 【IL-6阻害療法の基礎と臨床】IL-6とそのシグナル伝達系の分子基盤
松田 正; 室本 竜太; 鍛代 悠一; 織谷 健司, リウマチ科, 69, 1, 1, 12, Jan. 2023
(有)科学評論社, Japanese - Benzo[a]pyrene enhances IL-17-mediated responses by suppressing expression of Regnase-1 through AhR
成家康太; 室本竜太; 松田正, 日本薬学会年会要旨集(Web), 142nd, 2022 - 抗炎症脂質レゾルビンE2の1,4,7-トリエン-ベンゼン置換による安定等価体の創製研究
田中伸英; 村上侑斗; 平島洸基; 福田隼; 藤原広一; 渡邉瑞貴; 室本竜太; 松田正; 周東智, 反応と合成の進歩シンポジウム講演要旨集, 48th, 2022 - Benzo[a]pyrene enhances IL-17 response via AhR-mediated Regnase-1 suppression
室本竜太; 成家康太; 斎野由佳; 松田正, 日本免疫毒性学会学術年会講演要旨集, 28th, 2021 - STAT1 negatively regulates IκB-ζ gene transcription
室本竜太; 佐藤亜美; 松田正, 日本薬学会年会要旨集(Web), 141st, 2021 - Role of the adaptor molecule, Signal-transducing adaptor protein-2, for regulatory mechanisms of allergic responses
柏倉淳一; 松田正, 月刊アレルギーの臨床, 553, 2021 - Tyk2欠損マウスにおける免疫反応抑制にはマクロファージでのIL-10産生増強が関与する
室本 竜太; 平島 洸基; 美濃口 広弥; 松田 正, 日本薬学会年会要旨集, 140年会, 26Z, am13, Mar. 2020
(公社)日本薬学会, Japanese - Signal Transducing Adaptor Protein(STAP)-2はGVHD増悪に関与する
西東秀晃; 一井倫子; 戸田淳; 鍛代悠一; 室本竜太; 柏倉淳一; 斎藤宏大; 横田貴史; 柴山浩彦; 松田正; 織谷健司; 金倉譲; 金倉譲; 保仙直毅, 日本血液学会学術集会抄録(Web), 82nd, 2020 - 炎症収束脂質レゾルビンE2のスキップジエン構造をベンゼン環で置換した安定等価体創製研究
村上 侑斗; 福田 隼; 石村 航平; 平島 洸基; 室本 竜太; 渡邉 瑞貴; 松田 正; 周東 智, 日本薬学会年会要旨集, 139年会, 2, 96, 96, Mar. 2019
(公社)日本薬学会, Japanese - IL-17誘導性IκB-ζmRNA安定化へのTBK1の関与
斎野 由佳; 大垣内 優衣; 室本 竜太; 松田 正, 日本薬学会年会要旨集, 139年会, 3, 64, 64, Mar. 2019
(公社)日本薬学会, Japanese - トポテカンの新規標的である60SリボソームタンパクRPLAはDAMPsの放出およびがん免疫の活性化に関与する
山田駿介; 鍛代悠一; 室本竜太; 柏倉淳一; 松田正, 日本分子生物学会年会プログラム・要旨集(Web), 42nd, 2019 - Role of Signal Transducing Adaptor Protein-1 (STAP-1) in Chronic Myelogenous Leukemia Stem Cells
Jun Toda; Michiko Ichii; Hirohiko Shibayama; Hideaki Saito; Yuichi Kitai; Ryuta Muromoto; Jun-ichi Kashiwakura; Kodai Saitoh; Tadashi Matsuda; Kenji Oritani; Yuzuru Kanakura, BLOOD, 132, Nov. 2018
English, Summary international conference - 角化細胞におけるIL‐17誘導性IκB‐ζ発現機構の解析
室本竜太; 大垣内優衣; 斎野由佳; 佐藤亜美; 多和佳佑; 松田正, 日本免疫毒性学会学術年会講演要旨集, 25th, 66, Aug. 2018
Japanese - 新規α4インテグリンスプライシングバリアントは内在性α4インテグリン抑制分子である
重政歩美; 乾恭輔; 本田真知子; 松田正; 今重之, 日本薬学会年会要旨集(CD-ROM), 138th, 2018 - 自己免疫疾患における細胞外基質ネフロネクチンの関与
藤岡和征; 本田真知子; 松田正; 今重之, 日本薬学会年会要旨集(CD-ROM), 138th, 2018 - 細胞外基質ネフロネクチンに対するサンドイッチELISAシステムの構築
本田真知子; 李順姫; 松田正; 大槻剛巳; 今重之, 日本薬学会年会要旨集(CD-ROM), 138th, 2018 - Role of Signal Transducing Adaptor Protein (STAP) Family in Chronic Myelogenous Leukemia
Jun Toda; Michiko Ichii; Hirohiko Shibayama; Hideaki Saito; Yuichi Kitai; Ryuta Muromoto; Jun-ichi Kashiwakura; Kodai Saitoh; Tadashi Matsuda; Kenji Oritani; Yuzuru Kanakura, BLOOD, 130, Dec. 2017
English, Summary international conference - TYK2-mediated basal STAT3 activity and IL-17-induced mRNA stabilization coordinately dictate the expression level of I kappa B-zeta in keratinocytes
Ryuta Muromoto; Keisuke Tawa; Yui Ohgakiuchi; Tadashi Matsuda, CYTOKINE, 100, 90, 91, Dec. 2017
English, Summary international conference - P.acnes誘導性炎症・免疫応答の解析
松田正; 平島洸基; 齋藤浩大; 鍛代悠一; 柏倉淳一; 室本竜太, 微生物シンポジウム講演要旨集, 29th, 60‐61, 29 Aug. 2017
Japanese - Biochanin Aによる核内受容体RORγ活性化機構の解析
室本竜太; 高橋美妃; 小島弘幸; 武内伸治; 松田正, 衛生薬学・環境トキシコロジー講演要旨集, 2017, 237, 18 Aug. 2017
Japanese - JAKファミリーキナーゼ阻害が角化細胞のIL‐17応答に及ぼす影響
室本竜太; 多和佳佑; 大垣内優衣; 松田正, 日本免疫毒性学会学術年会講演要旨集, 24th, 70, Aug. 2017
Japanese - 微量オゾンによる炎症関連転写因子群のクロストークの解明—(有)オゾノサン・ジャパン研究助成費報告
松田 正, オゾン療法研究 = Ozone therapy research, 6, 75, 79, Jun. 2017
札幌 : 日本オゾン療法研究所, Japanese - SIGNAL TRANSDUCING ADAPTOR PROTEIN-1 (STAP-1) MAINTAINS CHRONIC MYELOID LEUKEMIC STEM CELLS
J. Toda; M. Ichii; K. Oritani; H. Saito; Y. Kitai; R. Muromoto; J. -I. Kashiwakura; K. Saitoh; T. Matsuda; Y. Kanakura, HAEMATOLOGICA, 102, 231, 231, Jun. 2017
English, Summary international conference - 炎症収束性脂質レゾルビンE1配座制限誘導体の設計と合成
石村航平; 福田隼; 室本竜太; 平島洸基; 渡邉瑞貴; 松田正; 周東智, 次世代を担う有機化学シンポジウム講演要旨集, 15th, 26‐27, 19 May 2017
Japanese - STAP-2によるT細胞活性化制御機構の解析
齋藤浩大; 今重之; 柏倉淳一; 室本竜太; 鍛代悠一; 関根勇一; 吉村昭彦; 織谷健司; 織谷健司; 松田正, 次世代を担う若手ファーマ・バイオフォーラム講演要旨集, 16th, 2017 - Concanavalin-A誘導性肝炎におけるSTAP-1の機能解析
伊原建; 齋藤浩大; 柏倉淳一; 今重之; 室本竜太; 鍛代悠一; 松田正, 次世代を担う若手ファーマ・バイオフォーラム講演要旨集, 16th, 2017 - シクロプロパン構造特性に基づくレゾルビンE2の安定等価体の創製研究
松原光太郎; 池田紘之; 石村航平; 平島洸基; 室本竜太; 松田正; 福田隼; 渡邉瑞貴; 周東智, 日本薬学会年会要旨集(CD-ROM), 137th, 2, ROMBUNNO.27R‐am10S, 120, 2017
(公社)日本薬学会, Japanese - トポテカンによる細胞死を介したDNA内包エクソソームの放出とSTING依存的がん免疫誘導機構の解明
鍛代悠一; 鍛代悠一; 川崎拓実; 末吉拓也; 小檜山康司; 石井健; 雛健; 審良静男; 松田正; 河合太郎, 日本薬学会年会要旨集(CD-ROM), 137th, ROMBUNNO.26PB‐pm021, 2017
Japanese - IL‐17誘導性IκB‐ζ発現におけるTyk2‐STAT3経路の役割
室本竜太; 多和佳佑; 松田正, 日本薬学会年会要旨集(CD-ROM), 137th, 3, ROMBUNNO.26PB‐am058, 138, 2017
(公社)日本薬学会, Japanese - 内因性炎症収束脂質レゾルビン類の創薬化学研究
池田紘之; 福田隼; 高倉夕季; 石村航平; 平島洸基; 平尾徹; 室本竜太; 渡邉瑞貴; 松田正; 周東智, メディシナルケミストリーシンポジウム講演要旨集, 34th, 143, 11 Nov. 2016
Japanese - Dupuytren拘縮における線維化メカニズムの解析
松井雄一郎; 今重之; 船越忠直; 河村太介; 亀田裕亮; 宮下友恵; 松田正; 岩崎倫政, 北海道整形災害外科学会, 130th, 2016 - Dupuytren拘縮の進行におけるインテグリンαvの関与
松井雄一郎; 今重之; 船越忠直; 河村太介; 亀田裕亮; 宮下友恵; 松田正; 岩崎倫政, 日本整形外科学会雑誌, 90, 2, 2016 - T細胞活性化及び免疫応答におけるSTAP-2の機能解析
齋藤浩大; 今重之; 今重之; 小澤清貴; 伊原建; 関根勇一; 室本竜太; 鍛代悠一; 吉村昭彦; 織谷健司; 松田正, 日本分子生物学会年会プログラム・要旨集(Web), 39th, 2016 - α9インテグリンの新規リガンドXCL1/Lymphotactinは自己免疫疾患増悪化に関与する
松本尚樹; 中鶴拓也; 宮下友惠; 乾恭輔; 蝦名佳貴; 今重之; 今重之; 松田正, 日本分子生物学会年会プログラム・要旨集(Web), 39th, 2016 - 悪性黒色腫の発症•進行•転移メカニズム
松田 正; 関根勇一; 鍛代悠一; 織谷健司, 次世代のがん治療薬・診断のための研究開発, 3, 10, 2016
Japanese - 自然免疫による癌細胞DNAの認識と抗腫瘍免疫発動機構の解析
鍛代悠一; 雛健; 川崎拓実; 末吉拓也; 小檜山康司; 石井健; 審良静男; 松田正; 河合太郎, 日本Cell Death学会学術集会プログラム抄録集, 25th, 64, 2016
Japanese - Arl5BによるMDA5依存的な抗ウイルス自然免疫応答の抑制機構の解明
鍛代悠一; 織大祐; 末吉拓也; 川崎拓実; 竹内理; 松田正; 審良静男; 河合太郎, 日本薬学会年会要旨集(CD-ROM), 136th, ROMBUNNO.29AB‐AM249, 2016
Japanese - ケラチノサイトのIL‐17応答におけるTYK2による間接的制御
室本竜太; 多和佳佑; 松田正, 日本薬学会年会要旨集(CD-ROM), 136th, 3, ROMBUNNO.29AB‐AM142, 127, 2016
(公社)日本薬学会, Japanese - 炎症収束性脂質・レゾルビンE2の安定等価体の創製
石村航平; 福田隼; 高倉夕季; 金田龍太郎; 平尾徹; 平島洸基; 室本竜太; 松田正; 阿部洋; 周東智, メディシナルケミストリーシンポジウム講演要旨集, 33rd, 78, 01 Nov. 2015
Japanese - 内因性炎症収束脂質レゾルビンE2安定等価体の創製
福田隼; 高倉夕季; 石村航平; 金田龍太郎; 平尾徹; 平島洸基; 室本竜太; 松田正; 阿部洋; 有澤光弘; 周東智, 反応と合成の進歩シンポジウム講演要旨集, 41st, 37, 09 Oct. 2015
Japanese - STAT3活性化を介したIL‐17A遺伝子発現に及ぼすバイオカニンAの影響
KOJIMA HIROYUKI; MUROMOTO RYUTA; TAKAHASHI MIKI; HIRAO TOORU; MATSUDA TADASHI, 日本免疫毒性学会学術年会講演要旨集, 22nd, 80, Aug. 2015
Japanese - 細胞表面へのホスホセリン提示可能なホスファチジルセリン二量体の設計と合成
佐藤耀; 川村周平; 平尾徹; 室本竜太; 福田隼; 阿部洋; 松田正; 周東智, 万有生命科学振興国際交流財団札幌シンポジウム, 27th, 42, 04 Jul. 2015
Japanese - Dupuytren拘縮におけるインテグリンの関与
松井雄一郎; 今重之; 船越忠直; 瓜田淳; 河村太介; 佃幸憲; 松田正; 岩崎倫政, 日本整形外科学会雑誌, 89, 2, 2015 - α4インテグリンスプライシングバリアントによるインテグリン機能調節機構の解明と創薬への発展
今重之; 紅露ひとみ; 中鶴拓也; 宮下友惠; 松本尚樹; 松田正, 日本薬学会年会要旨集(CD-ROM), 135th, 2015 - T細胞受容体シグナルにおけるSTAP-1及びSTAP-2の役割
小澤清貴; 齋藤浩大; 安次富大; 関根勇一; 室本竜太; 今重之; 松田正, 日本薬学会年会要旨集(CD-ROM), 135th, 2015 - 新規α9インテグリンリガンドLymphotactinの同定と機能解析
中鶴拓也; 松本尚樹; 紅露ひとみ; 松田正; 今重之, 日本薬学会年会要旨集(CD-ROM), 135th, 2015 - Dupuytren拘縮におけるインテグリンの関与
松井雄一郎; 船越忠直; 瓜田淳; 河村太介; 佃幸憲; 岩崎倫政; 今重之; 松田正, 北海道整形災害外科学会, 128th, 2015 - α9インテグリンバリアントSFα9結合分子に着目した新規自己免疫疾患治療薬の開発
松本尚樹; 中鶴拓也; 宮下友惠; 今重之; 松田正, 日本生化学会大会(Web), 88th, 2015 - 自己免疫疾患における新規カルシウム結合タンパク質,ネフロネクチンの役割
中鶴拓也; 今重之; 宮下友惠; 松本尚樹; 乾恭輔; 石川清; 瀬川辰也; 前田雅弘; 松田正, 日本生化学会大会(Web), 88th, 2015 - β8インテグリンスプライシングバリアントは新規TGF-βシグナル制御分子である
宮下友惠; 今重之; 中鶴拓也; 松本尚樹; 松井雄一郎; 岩崎倫政; 松田正, 日本生化学会大会(Web), 88th, 2015 - T細胞活性化におけるSTAP-1及びSTAP-2の役割
齋藤浩大; 今重之; 小澤清貴; 伊原建; 関根勇一; 室本竜太; 鍛代悠一; 吉村昭彦; 織谷健司; 松田正, 日本生化学会大会(Web), 88th, 2015 - IL−６とがん IL-6から見える景色
松田 正, Keynote R•A 先端医学社, 3, 3, 130, 132, 2015
先端医学社, Japanese, Introduction scientific journal - ファゴサイトーシス誘導性ホスファチジルセリン二量体類縁化合物の創製研究
SATO YO; KAWAMURA SHUHEI; HIRAO TOORU; MUROMOTO RYUTA; FUKUDA HAYATO; ABE HIROSHI; ABE HIROSHI; MATSUDA TADASHI; SHUTO SATOSHI, 日本薬学会年会要旨集(CD-ROM), 135th, ROMBUNNO.28T-AM12S, 2015
Japanese - ケラチノサイトのIL‐17応答調節におけるJAKファミリーチロシンキナーゼの役割
TAWA KEISUKE; MUROMOTO RYUTA; MATSUDA TADASHI, 日本薬学会年会要旨集(CD-ROM), 135th, 3, ROMBUNNO.28PB-PM107, 168, 2015
(公社)日本薬学会, Japanese - マクロファージの脂質代謝系制御におけるTyrosine kinase2(TYK2)の関与
HIRASHIMA KOKI; MUROMOTO RYUTA; MATSUDA TADASHI, 日本薬学会年会要旨集(CD-ROM), 135th, 3, ROMBUNNO.27W-PM10, 96, 2015
(公社)日本薬学会, Japanese - The Role of Signal-Transducing Adaptor Protein-2 in Early T Lymphopoiesis in Thymus
Michiko Ichii; Natsuko Fujita; Daisuke Okuzaki; Tetsuo Maeda; Yuichi Sekine; Shigeyuki Kon; Ryuta Muromoto; Kenji Oritani; Tadashi Matsuda; Yuzuru Kanakura, BLOOD, 124, 21, Dec. 2014
English, Summary international conference - REGULATION OF B LYMPHOPOIESIS BY SIGNAL-TRANSDUCING ADAPTOR PROTEIN-2, STAP-2
M. Ichii; K. Oritani; N. Fujita; N. Saitoh; Y. Sekine; R. Muromoto; S. Kon; K. Saitoh; T. Matsuda; Y. Kanakura, HAEMATOLOGICA, 99, 175, 175, Jun. 2014
English, Summary international conference - Y14 positively regulates TNF-alpha induced NF-kappa B transcriptional activity via interacting RIP1 and TRADD beyond an exon junction complex protein
Tadashi Matsuda; Sumihito Togi; Shigeyuki Kon; Yuichi Sekine; Ryuta Muromoto, FASEB JOURNAL, 28, 1, Apr. 2014
English, Summary international conference - 乾癬の発症とTYK2
ISHIZAKI MASAYUKI; MUROMOTO RYUTA; KON SHIGEYUKI; ORITANI KENJI; MATSUDA TADASHI, 月刊臨床免疫・アレルギー科, 61, 2, 214, 220, 25 Feb. 2014
科学評論社, Japanese - Dupuytren拘縮におけるインテグリンの関与
松井雄一郎; 今重之; 船越忠直; 瓜田淳; 河村太介; 佃幸憲; 松田正; 岩崎倫政, 日本整形外科学会雑誌, 88, 8, 2014 - Dupuytren拘縮におけるインテグリンの関与
松井雄一郎; 今重之; 船越忠直; 瓜田淳; 河村太介; 佃幸憲; 松田正; 岩崎倫政, 日本関節病学会誌, 33, 3, 2014 - 上皮がんにおけるBRKとSTAP-2の機能解析
岩上昌史; 久保果央莉; 室本竜太; 今重之; 松田正, 日本分子生物学会年会プログラム・要旨集(Web), 37th, 2014 - STAP-2の翻訳後修飾によるT細胞活性化調節機構の解析
安次富大; 今重之; 齋藤浩大; 関根勇一; 室本竜太; 織谷健司; 松田正, 日本分子生物学会年会プログラム・要旨集(Web), 37th, 2014 - 白血病細胞増殖におけるアダプター分子STAP-2制御性ケモカインレセプターの機能解析
久保果央莉; 岩上昌史; 室本竜太; 今重之; 関根勇一; 松田正, 日本分子生物学会年会プログラム・要旨集(Web), 37th, 2014 - A novel cryptic binding motif, LRSKSRSFQVSDEQY, in the C-terminal fragment of MMP-3/7-cleaved osteopontin as a novel ligand for α9β1 integrin is involved in the anti-type II collagen antibody-induced arthritis.
Shigeyuki Kon; Yosuke Nakayama; Naoki Matsumoto; Koyu Ito; Masashi Kanayama; Chiemi Kimura; Hitomi Kouro; Dai Ashitomi; Tadashi Matsuda; Toshimitsu Uede, PloS one, 9, 12, e116210, 2014, [International Magazine]
English - イソフラボン類によるSTAT3とRORγを介したIL‐17産生増強作用
小島弘幸; 室本竜太; 高橋美妃; 武内伸治; 松田正, 日本免疫毒性学会講演抄録集, 20th, 59, Aug. 2013
Japanese - An RNA binding protein, Y14 regulates TNF-alpha-induced NF-kappa B activation and IL-6 expression
Sumihito Togi; Ryuta Muromoto; Shigeyuki Kon; Yuichi Sekine; Tadashi Matsuda, JOURNAL OF IMMUNOLOGY, 190, May 2013
English, Summary international conference - 微量オゾンによる炎症関連転写因子群のクロストークの解明
けい澄仁; 今重之; 室本竜太; 松田正, 日本医療・環境オゾン学会研究講演会要旨集, 18th, 2013 - アダプタータンパク質STAP-2によるBRK活性化機構の解析
岩上昌史; 久保果央莉; 室本竜太; 今重之; 関根勇一; 松田正, 日本薬学会年会要旨集(CD-ROM), 133rd, 2013 - T細胞受容体シグナルにおけるアダプタータンパク質STAP-2の役割
齋藤浩大; 赤坂大地; 関根勇一; 室本竜太; 今重之; 松田正, 日本薬学会年会要旨集(CD-ROM), 133rd, 2013 - 細胞内配列の異なる新規変異型α4インテグリンの機能解析
紅露ひとみ; 今重之; 松田正, 日本薬学会年会要旨集(CD-ROM), 133rd, 2013 - アダプター分子STAP-2によるBCR-ABLチロシンキナーゼの制御機構
久保果央莉; 岩上昌史; 室本竜太; 今重之; 関根勇一; 松田正, 日本薬学会年会要旨集(CD-ROM), 133rd, 2013 - TNF-α/NF-κBシグナル経路におけるSTAT3とNF-κBのクロストークの解析
加藤聖弥; 研澄仁; 室本竜太; 今重之; 松田正, 日本薬学会年会要旨集(CD-ROM), 133rd, 2013 - 微量オゾンによる炎症関連転写因子群のクロストークの解明
とぎ澄仁; 坂内明日香; 今重之; 室本竜太; 松田正, 日本医療・環境オゾン学会会報, 20, 3, 2013 - アダプター分子STAP-2によるアポトーシス制御機構の解析
安次富大; 赤坂大地; 角地彩花; 関根勇一; 室本竜太; 今重之; 松田正, 日本薬学会年会要旨集(CD-ROM), 133rd, 2013 - 細胞内配列の異なる新規変異型α4インテグリンはα4インテグリン依存性細胞接着を抑制する
紅露ひとみ; 松本尚樹; 今重之; 松田正, 日本分子生物学会年会プログラム・要旨集(Web), 36th, 2013 - アダプター分子STAP-2による白血病細胞の増殖制御機構の解析
久保果央莉; 岩上昌史; 室本竜太; 今重之; 関根勇一; 松田正, 日本分子生物学会年会プログラム・要旨集(Web), 36th, 2013 - T細胞活性化におけるSTAP-2の機能解析
安次富大; 今重之; 斉藤浩大; 関根勇一; 室本竜太; 織谷健司; 松田正, 日本分子生物学会年会プログラム・要旨集(Web), 36th, 2013 - 結晶構造解析に向けた,乳がん特異的キナーゼBrkとアダプタータンパク質STAP‐2の機能解析
神田諒; 関根勇一; 前仲勝実; 松田正; 尾瀬農之, 日本分子生物学会年会プログラム・要旨集(Web), 36th, 2P-0302 (WEB ONLY), 2013
Japanese - 核内受容体RORα/γ依存的IL‐17産生に及ぼすイソフラボン類の影響
小島弘幸; 高橋美妃; 武田行正; 室本竜太; 武内伸治; ANTON M. Jetten; 松田正, 日本薬学会年会要旨集(CD-ROM), 133rd, ROMBUNNO.29AME-024, 2013
Japanese - RNA結合タンパクY14によるTNF‐α/NF‐κBシグナル制御機構の解析
研澄仁; 志賀要; 室本竜太; 今重之; 松田正, 日本薬学会年会要旨集(CD-ROM), 133rd, ROMBUNNO.28S-AM21S, 2013
Japanese - ケモカイン産生におけるTyk2の役割の解析
相馬悠樹; 大城裕也; 室本竜太; 松田正, 日本薬学会年会要旨集(CD-ROM), 133rd, ROMBUNNO.28S-PM22S, 2013
Japanese - イソフラボン類のIL-17産生増強作用
小島弘幸; 室本竜太; 高橋美妃; 武内伸治; 松田正, ImmunoTox Letter（日本免疫毒性学会誌）, 18, 2, 12, 14, 2013, [Invited]
Japanese, Report scientific journal - ダイオキシン受容体を介したIL‐17遺伝子発現に及ぼす環境化学物質の影響
小島弘幸; 室本竜太; 高橋美妃; 武内伸治; 松田正, 日本内分泌かく乱化学物質学会研究発表会要旨集, 15th, 45, 18 Dec. 2012
Japanese - 分子標的薬の作用機序・薬理作用 がん関連標的分子・標的経路 JAK/STATシグナル伝達経路を標的とした分子標的薬
MATSUDA TADASHI; KON SHIGEYUKI; MUROMOTO RYUTA, 日本臨床, 70, 45, 51, 20 Nov. 2012
Japanese - マウスEL4細胞のIL‐17及びIL‐22遺伝子発現に及ぼすAhRアゴニストの影響
小島弘幸; 室本竜太; 高橋美妃; 武内伸治; 松田正, 日本免疫毒性学会講演抄録集, 19th, 65, Aug. 2012
Japanese - A novel murine alpha 4 integrin splicing variant is a specific receptor for VCAM-1
Shigeyuki Kon; Hitomi Kouro; Tadashi Matsuda, JOURNAL OF IMMUNOLOGY, 188, May 2012
English, Summary international conference - ZIPK modulates canonical Wnt/beta-catenin signaling through interaction with NLK/TCF4
Sumihito Togi; Ryuta Muromoto; Tadashi Matsuda, FASEB JOURNAL, 26, Apr. 2012
English, Summary international conference - 炎症性サイトカインIL‐17産生に及ぼすBiochanin Aの影響に関する研究
高橋美妃; 室本竜太; 小島弘幸; 武内伸治; 松田正, 日本薬学会年会要旨集, 132nd, 3, 98, 05 Mar. 2012
Japanese - 環境化学物質における核内受容体RORα/γ活性の探索とIL‐17遺伝子発現への影響
小島弘幸; 室本竜太; 高橋美妃; 武内伸治; 松田正, 日本薬学会年会要旨集, 132nd, 3, 268, 05 Mar. 2012
Japanese - メラノーマがん細胞転移におけるアダプター分子STAP‐2の役割
角地彩花; 赤坂大地; 関根勇一; 今重之; 室本竜太; 松田正, 日本薬学会年会要旨集, 132nd, 3, 113, 05 Mar. 2012
Japanese - STAP-2によるT細胞抗原受容体シグナル伝達制御機構の解析
赤坂大地; 角地彩花; 今重之; 関根勇一; 松田正, 日本薬学会年会要旨集, 132nd, 3, 2012 - T細胞受容体シグナルにおけるアダプタータンパク質STAP-2の役割
今重之; 赤坂大地; 関根勇一; 室本竜太; 吉村昭彦; 松田正, 日本分子生物学会年会プログラム・要旨集(Web), 35th, 2012 - RORα/γ依存的なIL‐17産生に及ぼすBiochanin Aの影響
小島弘幸; 室本竜太; 高橋美妃; 武内伸治; 松田正, 日本内分泌かく乱化学物質学会研究発表会要旨集, 14th, 40, 01 Dec. 2011
Japanese - アダプター分子STAP‐2よる活性化誘導性細胞死(AICD)制御機構の解析
山本千香子; 関根勇一; 室本竜太; 松田正, 次世代を担う若手ファーマ・バイオフォーラム講演要旨集, 10th, 30, Sep. 2011
Japanese - 新規乳癌治療標的としてのチロシンキナーゼBRKの機能解析
水嶋明宏; 池田収; 関根勇一; 関根勇一; 室本竜太; 室本竜太; 松田正; 松田正, 次世代を担う若手ファーマ・バイオフォーラム講演要旨集, 10th, 75, Sep. 2011
Japanese - RORγt依存的なIL‐17遺伝子発現誘導に対するイソフラボン類の影響
小島弘幸; 室本竜太; 高橋美妃; 武内伸治; 松田正, 日本免疫毒性学会講演抄録集, 18th, 73, Aug. 2011
Japanese - Adaptor protein, signal-transducing adaptor protein-2 regulates T-cell functions
関根 勇一; 松田 正, Clinical immunology & allergology, 55, 5, 507, 514, May 2011
科学評論社, Japanese - TYK2とJun activation domain‐binding protein 1(JAB1)の機能的相互作用の解析
室本竜太; 高橋美妃; 坪内真知子; 関根勇一; 南保明日香; 松田正, 日本薬学会年会要旨集, 131st, 3, 102, 05 Mar. 2011
Japanese - 核内コリプレッサーKAP1によるSTAT3を介したTNF‐α/NF‐κBシグナル制御機構の解析
硎澄仁; 上谷晋也; 池田収; 川上志保; 関根勇一; 室本竜太; 南保明日香; 松田正, 日本薬学会年会要旨集, 131st, 3, 136, Mar. 2011
Japanese - Regulatory proteins of IL-6/STAT3 signaling pathway: Daxx, KAP1 and STAP-2
松田 正; 室本 竜太; 関根 勇一, 医学のあゆみ, 234, 5, 401, 407, 31 Jul. 2010
医歯薬出版, Japanese - IN VIVO FUNCTION OF A NOVEL ADAPTOR PROTEIN STAP2 IN THE PROGRESS OF INFLAMMATION
N. Fujita; K. Oritani; T. Yokota; N. Saitoh; T. Sudo; Y. Sekina; T. Matsuda; Y. Kanakura, HAEMATOLOGICA-THE HEMATOLOGY JOURNAL, 95, 667, 667, Jun. 2010
English, Summary international conference - KAP1 regulates TNF-Induced NF-kappaB transcriptional activity by influencing the interactions between p300 and NF-kappaB
Sumihito Togi; Shinya Kamitani; Shiho Kawakami; Osamu Ikeda; Ryuta Muromoto; Yuichi Sekine; Asuka Nanbo; Tadashi Matsuda, FASEB JOURNAL, 24, Apr. 2010
English, Summary international conference - BS69 negatively regulates the canonical NF-kappaB activation induced by Epstein-Barr virus-derived LMP1
Osamu Ikeda; Yuichi Sekine; Ryuta Muromoto; Asuka Nanbo; Tadashi Matsuda, FASEB JOURNAL, 24, Apr. 2010
English, Summary international conference - STAP-2 regulates integrin-mediated T-cell adhesion through protein degradation of FAK
Tadashi Matsuda; Osamu Ikeda; Yuichi Sekine, FASEB JOURNAL, 22, Apr. 2008
English, Summary international conference - インターフェロンによるB細胞の増殖制御
室本竜太; 織谷健司; 下田和哉; 松田正, 月刊臨床免疫・アレルギー科, 47, 6, 735-744, 744, 25 Jun. 2007
科学評論社, Japanese - インターフェロン誘導性タンパク質Daxxによる転写因子STAT3の機能制御
室本竜太; 北本竜生; 中嶋麻衣子; 杉山憲司; 石田雅人; 松田正, 日本薬学会年会要旨集, 127th, 2, 17, 05 Mar. 2007
Japanese - Regulation of the Epstein-Barr virus LMP1-mediated NF-kappaB signaling pathway by a novel adaptor protein STAP-2
Osamu Ikeda; Yuichi Sekine; Teruhito Yasui; Suita Kenji Sugiyma; Kenji Oritani; Suita Akihiko Yoshimura; Tadashi Matsuda, CLINICAL IMMUNOLOGY, 123, S33, S34, 2007
English, Summary international conference - Regulation of the STAT3-mediated signaling by Daxx
Kenji Sugiyama; Ryuta Muromoto; Masato Ishida; Yuichi Sekine; Kenji Oritani; Tadashi Matsuda, CLINICAL IMMUNOLOGY, 123, S159, S159, 2007
English, Summary international conference - ウイルス感染と宿主応答・宿主側の要因 新規アダプター分子STAP-2とEBウイルス産物LMP1の機能的相互作用の解析
池田 収; 関根 勇一; 辻 暁司; 安居 輝人; 杉山 憲司; 吉村 昭彦; 松田 正, 日本免疫学会総会・学術集会記録, 36, 206, 206, Nov. 2006
(NPO)日本免疫学会, Japanese - ZIPKとNLKの機能的相互作用の解析
渡部匡史; 室本竜太; 佐藤紀子; 杉山憲司; 松田正, 日本薬学会年会要旨集, 126th, 3, 81, 81, 06 Mar. 2006
(公社)日本薬学会, Japanese - Modulation of toll-like receptor 4 signaling by a novel adaptor protein STAP-2 in macrophages
Y Sekine; S Tsuji; O Ikeda; K Sugiyama; S Akira; A Yoshimiura; T Matsuda, FASEB JOURNAL, 20, 4, A114, A114, Mar. 2006
English, Summary international conference - Physical and functional interactions between Daxx and STAT3
T Matsuda; R Muromoto; K Nakao; T Watanabe; N Sato; Y Sekine; K Sugiyma, FASEB JOURNAL, 20, 4, A533, A533, Mar. 2006
English, Summary international conference - DaxxによるSTAT3転写活性化抑制機構の解析
中尾圭; 室本竜太; 杉山憲司; 渡部匡史; 織谷健司; 下田和哉; 松田正, 日本免疫学会総会・学術集会記録, 35, 285, 285, 15 Nov. 2005
(NPO)日本免疫学会, Japanese - アダプター分子STAP‐2によるSTAT蛋白の機能調節
SEKINE YUICHI; TSUJI SATOSHI; IKEDA OSAMU; MATSUDA TADASHI, 臨床免疫, 44, 3, 339, 344, 25 Sep. 2005
科学評論社, Japanese - A novel mutation in the juxtamembrane intracellular sequence of the granulocyte colony-stimulating factor (G-CSF) receptor gene in a patient with severe congenital neutropenia augments G-CSF proliferation activity but not through the MAP kinase cascade
T Yokoyama; S Okamura; Y Asano; K Kamezaki; A Numata; H Kakumitsu; K Shide; H Nakashima; T Kanaji; Y Sekine; Y Mizuno; J Okamura; T Matsuda; M Harada; Y Niho; K Shimoda, INTERNATIONAL JOURNAL OF HEMATOLOGY, 82, 1, 28, 34, Jul. 2005
English - Transgenic mice overexpressing murine thrombopoietin develop myelofibrosis and osteosclerosis
B Kakumitsu; B Kamezaki; B Shimoda; K Karube; T Haro; A Numata; K Shide; T Matsuda; K Oshima; M Harada, LEUKEMIA RESEARCH, 29, 7, 761, 769, Jul. 2005
English - Differential effects of phthalate esters on transcriptional activities via human estrogen receptors alpha and beta, and androgen receptor
S Takeuchi; M Iida; S Kobayashi; K Jin; T Matsuda; H Kojima, TOXICOLOGY, 210, 2-3, 223, 233, Jun. 2005
English - Roles for lysine residues of the MH2 domain of Smad3 in transforming growth factor-beta e signaling
S Imoto; K Sugiyama; Y Sekine; T Matsuda, FEBS LETTERS, 579, 13, 2853, 2862, May 2005
English - Physical and functional interactions between STAP-2/BKS and STAT5
Y Sekine; T Yamamoto; T Yumioka; K Sugiyama; S Tsuji; K Oritani; K Shimoda; M Minoguchi; A Yoshimura; T Matsuda, JOURNAL OF BIOLOGICAL CHEMISTRY, 280, 9, 8188, 8196, Mar. 2005
English - Roles of a STAT3 kinase in STAT3-mediated signaling
N Sato; Y Kamata; K Sugiyama; Y Sekine; T Matsuda, FASEB JOURNAL, 19, 5, A1419, A1419, Mar. 2005
English, Summary international conference - Roles of a STAT binding protein in cytokine signaling
T Okayama; N Sato; K Sugiyama; T Matsuda, FASEB JOURNAL, 19, 5, A1420, A1420, Mar. 2005
English, Summary international conference - Roles of Stat3 and ERK in G-CSF signaling
K Kamezaki; K Shimoda; A Numata; T Haro; H Kakumitsu; M Yoshie; Y Yamamoto; K Takeda; T Matsuda; M Akira; K Ogawa; O Harada, STEM CELLS, 23, 2, 252, 263, Feb. 2005
English - サイトカインシグナル伝達系とその制御―シグナル伝達分子STAT3を中心に―
SATO NORIKO; SEKINE YUICHI; MATSUDA TADASHI, 日本応用酵素協会誌, 39, 11, 17, 01 Feb. 2005
Japanese - Cytokine induction by a bacterial DNA-specific modified base
Biochem. Biophys. Res. Commun., 326:777-781, 2005 - Daxxの変異体によるインターフェロンのBリンパ球前駆細胞増殖抑制活性の阻害
室本竜太; 杉山憲司; 織谷健司; 下田和哉; 松田正, 日本免疫学会総会・学術集会記録, 34, 191, 05 Nov. 2004
Japanese - Bacterial endotoxin induces IL-20 expression in the glial cells
T Hosoi; S Wada; S Suzuki; Y Okuma; S Akira; T Matsuda; Y Nomura, MOLECULAR BRAIN RESEARCH, 130, 1-2, 23, 29, Nov. 2004
English - The roles of stat3 and ERK in G-CSF signaling.
K Kamezaki; K Shimoda; A Numata; M Yoshie; M Yamamoto; K Takeda; T Matsuda; S Akira; K Ogawa; M Harada, BLOOD, 104, 11, 597A, 597A, Nov. 2004
English, Summary international conference - Differential expression of integrin subunits in DU-145/AR prostate cancer cells
O Nagakawa; T Akashi; Y Hayakawa; A Junicho; K Koizumi; Y Fujiuchi; Y Furuya; T Matsuda; H Fuse; Saiki, I, ONCOLOGY REPORTS, 12, 4, 837, 841, Oct. 2004
English - Hapten-induced contact hypersensitivity is enhanced in Tyk2-deficient mice
M Hosogi; H Tonogaito; A Aioi; K Hamada; K Shimoda; R Muromoto; T Matsuda; Y Miyachi, JOURNAL OF DERMATOLOGICAL SCIENCE, 36, 1, 51, 56, Oct. 2004
English - Bacterial endotoxin induces STAT3 activation in the mouse brain
T Hosoi; Y Okuma; T Kawagishi; Qi, X; T Matsuda; Y Nomura, BRAIN RESEARCH, 1023, 1, 48, 53, Oct. 2004
English - The role of Tyk2, Stat1 and Stat4 in LPS-induced endotoxin signals
K Kamezaki; K Shimoda; A Numata; T Matsuda; K Nakayama; M Harada, INTERNATIONAL IMMUNOLOGY, 16, 8, 1173, 1179, Aug. 2004
English - Influence of endoplasmic reticulum stress on iNOS induction in glial cells
T Hosoi; Y Okuma; M Takakuwa; T Matsuda; Y Nomura, NITRIC OXIDE-BIOLOGY AND CHEMISTRY, 11, 1, 109, 109, Aug. 2004
English, Summary international conference - Tyrosine kinase 2 interacts with and phosphorylates receptor for-activated c kinase-1, a WD motif-containing protein
T Haro; K Shimoda; H Kakumitsu; K Kamezaki; A Numata; F Ishikawa; Y Sekine; R Muromoto; T Matsuda; M Harada, JOURNAL OF IMMUNOLOGY, 173, 2, 1151, 1157, Jul. 2004
English - The RING domain of PIASy is involved in the suppression of bone morphogenetic protein-signaling pathway
S Imoto; K Sugiyama; T Yamamoto; T Matsuda, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 319, 1, 275, 282, Jun. 2004
English - Physical and functional interactions between Daxx and TSG101
R Muromoto; K Sugiyama; T Yamamoto; K Oritani; K Shimoda; T Matsuda, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 316, 3, 827, 833, Apr. 2004
English - Cross-talk between endocrine-disrupting chemicals and cytokine signaling through estrogen receptors
Y Sekine; T Yamamoto; T Yumioka; S Imoto; H Kojima; T Matsuda, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 315, 3, 692, 698, Mar. 2004
English - Physical and functional interactions between Daxx and DNA methyltransferase 1-associated protein, DMAP1
R Muromoto; K Sugiyama; A Takachi; S Imoto; N Sato; T Yamamoto; K Oritani; K Shimoda; T Matsuda, JOURNAL OF IMMUNOLOGY, 172, 5, 2985, 2993, Mar. 2004
English - TEL-Syk fusion constitutively activates PI3-K/Akt, MAPK and JAK2-independent STAT5 signal pathways
T Kanie; A Abe; T Matsuda; Y Kuno; M Towatari; T Yamamoto; H Saito; N Emi; T Naoe, LEUKEMIA, 18, 3, 548, 555, Mar. 2004
English - Molecular dynamics of STAT3 on IL-6 signaling pathway in living cells
Biochem. Biophys. Res. Commun., 324, 1264-1273, 2004 - Involvement of NF-kappa B in TGF-beta-mediated suppression of IL-4 signaling
T Yamamoto; S Imoto; Y Sekine; K Sugiyama; T Akimoto; A Muraguchi; T Matsuda, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 313, 3, 627, 634, Jan. 2004
English - The mechanisms of bacterial endotoxin-induced endoplasmic reticulum stress response
T Hosoi; Y Okuma; M Takakuwa; T Matsuda; Y Nomura, JOURNAL OF PHARMACOLOGICAL SCIENCES, 94, 299P, 299P, 2004
English, Summary international conference - Limitin, an interferon-like cytokine, transduces inhibitory signals on B-cell growth through activation of Tyk2, but not Stat1, followed by induction and nuclear translocation of Daxx
K Aoki; K Shimoda; K Oritani; T Matsuda; K Kamezaki; R Muromoto; A Numata; S Tamiya; T Haro; F Ishikawa; K Takase; T Yamamoto; T Yumioka; T Miyamoto; K Nagafuji; H Gondo; S Nagafuchi; K Nakayama; M Harada, EXPERIMENTAL HEMATOLOGY, 31, 12, 1317, 1322, Dec. 2003
English - サイトカインシグナル伝達分子STAT3に会合する新規分子の同定
佐藤紀子; 杉山憲司; 石黒真琴; 井本世祐; 室本竜太; 山本哲也; 松田正, 日本免疫学会総会・学術集会記録, 33, 257, 05 Nov. 2003
Japanese - Bリンパ球前駆細胞の増殖抑制に関与するDaxxの新規結合分子同定と解析
室本竜太; 杉山憲司; 井本世祐; 佐藤紀子; 山本哲也; 織谷健司; 下田和哉; 松田正, 日本免疫学会総会・学術集会記録, 33, 264, 05 Nov. 2003
Japanese - Intracellular signal transduction of interferon on the suppression of hematopoietic progenitor cell growth.
K Kamezaki; K Kato; K Shimoda; A Numata; T Haro; K Aoki; F Ishikawa; K Takase; H Ariyama; T Matsuda; T Miyamoto; K Nagafuji; H Gondo; K Nakayama; M Harada, BLOOD, 102, 11, 167B, 167B, Nov. 2003
English, Summary international conference - Regulation of transforming growth factor-beta signaling by protein inhibitor of activated STAT, PIASy through Smad3
S Imoto; K Sugiyama; R Muromoto; N Sato; T Yamamoto; T Matsuda, JOURNAL OF BIOLOGICAL CHEMISTRY, 278, 36, 34253, 34258, Sep. 2003
English - Regulation of transforming growth factor-beta signaling by protein inhibitor of activated STAT, PIASy through Smad3
S Imoto; K Sugiyama; R Muromoto; N Sato; T Yamamoto; T Matsuda, JOURNAL OF BIOLOGICAL CHEMISTRY, 278, 36, 34253, 34258, Sep. 2003
English - Regulation of Fc epsilon RI-mediated signaling by an adaptor protein STAP-2/BSK in rat basophilic leukemia RBL-2H3 cells
T Yamamoto; T Yumioka; Y Sekine; N Sato; M Minoguchi; A Yoshimura; T Matsuda, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 306, 3, 767, 773, Jul. 2003
English - Regulation of Fc epsilon RI-mediated signaling by an adaptor protein STAP-2/BSK in rat basophilic leukemia RBL-2H3 cells
T Yamamoto; T Yumioka; Y Sekine; N Sato; M Minoguchi; A Yoshimura; T Matsuda, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 306, 3, 767, 773, Jul. 2003
English - Molecular interactions between STAT3 and protein inhibitor of activated STAT3, and androgen receptor
T Yamamoto; N Sato; Y Sekine; T Yumioka; S Imoto; A Junicho; H Fuse; T Matsuda, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 306, 2, 610, 615, Jun. 2003
English - Daxx enhances Fas-mediated apoptosis in a murine pro-B cell line, BAF3
R Muromoto; T Yamamoto; T Yumioka; Y Sekine; K Sugiyama; K Shimoda; K Oritani; T Matsuda, FEBS LETTERS, 540, 1-3, 223, 228, Apr. 2003
English - STAP-2/BKS, an adaptor/docking protein, modulates STAT3 activation in acute-phase response through its YXXQ motif
M Minoguchi; S Minoguchi; D Aki; A Joo; T Yamamoto; T Yumioka; T Matsuda; A Yoshimura, JOURNAL OF BIOLOGICAL CHEMISTRY, 278, 13, 11182, 11189, Mar. 2003
English - STAP-2/BKS, an adaptor/docking protein, modulates STAT3 activation in acute-phase response through its YXXQ motif
M Minoguchi; S Minoguchi; D Aki; A Joo; T Yamamoto; T Yumioka; T Matsuda; A Yoshimura, JOURNAL OF BIOLOGICAL CHEMISTRY, 278, 13, 11182, 11189, Mar. 2003
English - Molecular interactions between STAT3 and protein inhibitor of activated STAT3, and androgen receptor
Biochem.Biophys.Ress.Commun, 360, 767, 773, 2003 - Involvement of heat-shock protein 90 in the interleukin-6-mediated signaling pathway through STAT3
N Sato; T Yamamoto; Y Sekine; T Yumioka; A Junicho; H Fuse; T Matsuda, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 300, 4, 847, 852, Jan. 2003
English - Mapping of the sites responsible for factor I-cofactor activity for cleavage of C3b and C4b on human C4b-binding protein (C4bp) by deletion mutagenesis
A Fukui; T Yuasa-Nakagawa; Y Murakami; K Funami; N Kishi; T Matsuda; T Fujita; T Seya; S Nagasawa, JOURNAL OF BIOCHEMISTRY, 132, 5, 719, 728, Nov. 2002
English - Tyk2 is required for the induction and nuclear translocation of Daxx which regulates interferon-alpha-induced suppression of B lymphocyte formation.
K Shimoda; K Kamesaki; A Numata; K Aoki; T Matsuda; K Oritani; K Kato; K Takase; R Imamura; T Miyamoto; K Nagafuji; H Gondo; KI Nakayama; M Harada, BLOOD, 100, 11, 190A, 190A, Nov. 2002
English, Summary international conference - AML1/MTG8 leukemic protein induces activation of STAT3
K Aoki; K Shimoda; T Matsuda; A Numata; K Kamezaki; K Takase; T Haro; T Miyamoto; K Nagafuji; H Gondo; M Harada, BLOOD, 100, 11, 209B, 209B, Nov. 2002
English, Summary international conference - リミチンによるBリンパ球前駆細胞アポトーシスの誘導とDaxxの関与
松田正; 山本哲也; 室本竜太; 織谷健司; 下田和哉, 日本免疫学会総会・学術集会記録, 32, 173, 31 Oct. 2002
Japanese - Lymphoid enhancer-binding factor-1 binds and activates the recombination-activating gene-2 promoter together with c-Myb and Pax-5 in immature B cells
ZX Jin; H Kishi; XC Wei; T Matsuda; S Saito; A Muraguchi, JOURNAL OF IMMUNOLOGY, 169, 7, 3783, 3792, Oct. 2002
English - The nuclear isoform of protein-tyrosine phosphatase TC-PTP regulates interleukin-6-mediated signaling pathway through STAT3 dephosphorylation
T Yamamoto; Y Sekine; K Kashima; A Kubota; N Sato; N Aoki; T Matsuda, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 297, 4, 811, 817, Oct. 2002
English - 樹状細胞におけるCD40発現の選択的制御
飯島 則文; 柳川 芳毅; 松田 正; 小野江 和則, 日本免疫学会総会・学術集会記録, 32, 54, 54, Oct. 2002
(NPO)日本免疫学会, Japanese - Characterization of chromatin structure and enhancer elements for murine recombination activating gene-2
XC Wei; H Kishi; ZX Jin; WP Zhao; S Kondo; T Matsuda; S Saito; A Muraguchi, JOURNAL OF IMMUNOLOGY, 169, 2, 873, 881, Jul. 2002
English - Cross-talk between bone morphogenic proteins and estrogen receptor signaling
T Yamamoto; F Saatcioglu; T Matsuda, ENDOCRINOLOGY, 143, 7, 2635, 2642, Jul. 2002
English - The regulation of DNAse activities in subcellular compartments of activated thymocytes
T Nagata; H Kishi; QL Liu; T Matsuda; T Imanaka; K Tsukada; D Kang; A Muraguchi, IMMUNOLOGY, 105, 4, 399, 406, Apr. 2002
English - Partial impairment of interleukin-12 (IL-12) and IL-18 signaling in Tyk2-deficient mice
K Shimoda; H Tsutsui; K Aoki; K Kato; T Matsuda; A Numata; K Takase; T Yamamoto; H Nukina; T Hoshino; Y Asano; H Gondo; T Okamura; S Okamura; KI Nakayama; K Nakanishi; Y Niho; M Harada, BLOOD, 99, 6, 2094, 2099, Mar. 2002
English - Vasoactive intestinal peptide (VIP) enhances the cell motility of androgen receptor-transfected DU-145 prostate cancer cells (DU-145/AR)
O Nagakawa; J Murata; A Junicho; T Matsuda; Y Fujiuchi; H Fuse; Saiki, I, CANCER LETTERS, 176, 1, 93, 99, Feb. 2002
English - LEF-1 binds and activates the recombination-activating gene-2 promoter together with c-Myb and Pax-5 in immature B cells.
J. Immunol., 169,3783-3792, 2002 - Cooperative binding of c-Myb and Pax-5 activates the RAG-2 promoter in immature B cells
H Kishi; ZX Jin; XC Wei; T Nagata; T Matsuda; S Saito; A Muraguchi, BLOOD, 99, 2, 576, 583, Jan. 2002
English - Constitutive STAT5 activation by the TEL-SYK fusion gene from a patient with myelodysplastic syndrome.
T Kanie; A Abe; T Matsuda; Y Kuno; M Towatari; N Emi; H Saito, BLOOD, 98, 11, 563A, 563A, Nov. 2001
English, Summary international conference - Cross-talk between signal transducer and activator of transcription 3 and androgen receptor signaling in prostate carcinoma cells
T Matsuda; A Junicho; T Yamamoto; H Kishi; K Korkmaz; F Saatcioglu; H Fuse; A Muraguchi, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 283, 1, 179, 187, Apr. 2001, ［Internationally co-authored］
English - Cross-talk between IL-6 and TGF-beta signaling in hepatoma cells
T Yamamoto; T Matsuda; A Muraguchi; K Miyazono; M Kawabata, FEBS LETTERS, 492, 3, 247, 253, Mar. 2001
English - Cross-talk between IL-6 and TGF-beta signaling in hepatoma cells
T Yamamoto; T Matsuda; A Muraguchi; K Miyazono; M Kawabata, FEBS LETTERS, 492, 3, 247, 253, Mar. 2001
English - Hematopoietic cell-specific adapter proteins, SLP-76 and BLNK, effectively activate NF-AT as well as NF-kappa B by Syk and Tec PTKs in non-lymphoid cell lines
T Yamamoto; T Matsuda; A Junicho; H Kishi; A Yoshimura; A Muraguchi, FEBS LETTERS, 491, 3, 272, 278, Mar. 2001
English - 前立腺癌細胞におけるProtein inhibitor of activated STAT3(PIAS3)によるアンドロゲン受容体の負の制御機構
十二町 明; 松田 正; 永川 修; 村口 篤; 布施 秀樹, 日本泌尿器科學會雜誌, 92, 2, 267, 267, 20 Feb. 2001
社団法人日本泌尿器科学会, Japanese - Cross-talk between TGF-beta and estrogen receptor signaling through Smad3.
J. Biol. Chem., 276: 42907-42914, 2001 - Cross-talk between TGF-beta and estrogen receptor signaling through Smad3.
J. Biol. Chem., 276: 42907-42914, 2001 - Cross-talk between signal transducer and activator of transcription 3 and estrogen receptor signaling
T Yamamoto; T Matsuda; A Junicho; H Kishi; F Saatcioglu; A Muraguchi, FEBS LETTERS, 486, 2, 143, 148, Dec. 2000, ［Internationally co-authored］, [International Magazine]
English - Protein inhibitor of activated STAT3 regulates androgen receptor signaling in prostate carcinoma cells
A Junicho; T Matsuda; T Yamamoto; H Kishi; K Korkmaz; F Saatcioglu; H Fuse; A Muraguchi, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 278, 1, 9, 13, Nov. 2000, ［Internationally co-authored］, [International Magazine]
English - Tyk2 plays a restricted role in IFN alpha signaling, although it is required for IL-12-mediated T cell function
K Shimoda; K Kato; K Aoki; T Matsuda; A Miyamoto; M Shibamori; M Yamashita; A Numata; K Takase; S Kobayashi; S Shibata; Y Asano; H Gondo; K Sekiguchi; K Nakayama; T Nakayama; T Okamura; S Okamura; Y Niho; K Nakayama, IMMUNITY, 13, 4, 561, 571, Oct. 2000
English - Possible involvement of cyclophilin B and caspase-activated deoxyribonuclease in the induction of chromosomal DNA degradation in TCR-stimulated thymocytes
T Nagata; H Kishi; QL Lin; T Yoshino; T Matsuda; ZX Jin; K Murayama; K Tsukada; A Muraguchi, JOURNAL OF IMMUNOLOGY, 165, 8, 4281, 4289, Oct. 2000
English - Lineage-specific regulation of the murine RAG-2 promoter: GATA-3 in T cells and Pax-5 in B cells
H Kishi; XC Wei; ZX Jin; Y Fujishiro; T Nagata; T Matsuda; A Muraguchi, BLOOD, 95, 12, 3845, 3852, Jun. 2000
English - SOCS-1 can suppress CD3 zeta- and Syk-mediated NF-AT activation in a non-lymphoid cell line
T Matsuda; T Yamamoto; H Kishi; A Yoshimura; A Muraguchi, FEBS LETTERS, 472, 2-3, 235, 240, Apr. 2000
English - Apoptosis-inducing activity in a microsomal fraction of TCR-stimulated mouse thymocytes
T Nagata; H Kishi; KL Lyu; T Yoshino; T Matsuda; A Muraguchi, FASEB JOURNAL, 14, 6, A923, A923, Apr. 2000
English, Summary international conference - IL-6シグナル伝達系とアンドロゲン受容体のクロストーク
十二町 明; 松田 正; 村口 篤; 永川 修; 布施 秀樹, 日本泌尿器科學會雜誌, 91, 3, 346, 346, 20 Mar. 2000
社団法人日本泌尿器科学会, Japanese - Lactate dehydrogenase A-dependent surface expression of immature thymocyte antigen-1: an implication for a novel trafficking function of lactate dehydrogenase-A during T cell development
Y Fujishiro; H Kishi; T Matsuda; H Fuse; A Muraguchi, EUROPEAN JOURNAL OF IMMUNOLOGY, 30, 2, 516, 524, Feb. 2000
English - 胸腺T細胞のアポトーシス誘導とその制御
臨床免疫, 34, 424-433, 2000 - Distinct factors, GATA-3 and Pax-5, may reciprocally regulate the murine RAG2 promoter in T-and B-lineage cells.
Blood., 95: 3845-3852, 2000 - Distinct factors, GATA-3 and Pax-5, may reciprocally regulate the murine RAG2 promoter in T-and B-lineage cells.
Blood., 95: 3845-3852, 2000 - A bone marrow-derived stroma cell line, ST2, can support the differentiation of fetal thymocytes from the CD4(-) CD8(-) double negative to the CD4(+) CD8(+) double positive differentiation stage in vitro
JJ Tong; H Kishi; T Matsuda; A Muraguchi, IMMUNOLOGY, 97, 4, 672, 678, Aug. 1999
English - The JAK-binding protein JAB inhibits Janus tyrosine kinase activity through binding in the activation loop
H Yasukawa; H Misawa; H Sakamoto; M Masuhara; A Sasaki; T Wakioka; S Ohtsuka; T Imaizumi; T Matsuda; JN Ihle; A Yoshimura, EMBO JOURNAL, 18, 5, 1309, 1320, Mar. 1999, ［Internationally co-authored］
English - Regulation of JAK kinase activity by an intrinsic kinase inhibitor, JAB
H Yasukawa; H Misawa; M Masuhara; H Sakamoto; H Ohgusu; T Matsuda; JN Ihle; A Yoshimura, CIRCULATION, 98, 17, 119, 119, Oct. 1998
English, Summary international conference - Activation of Jak2 catalytic activity requires phosphorylation of Y-1007 in the kinase activation loop
J Feng; BA Witthuhn; T Matsuda; F Kohlhuber; IM Kerr; JN Ihle, MOLECULAR AND CELLULAR BIOLOGY, 17, 5, 2497, 2501, May 1997, ［Internationally co-authored］, [International Magazine]
English - Phosphorylation of tyrosine 1007 is required for the activation of Jak2.
J Feng; BA Witthuhn; T Matsuda; IM Kerr; JN Ihle, BLOOD, 88, 10, 1777, 1777, Nov. 1996
English, Summary international conference - ACTIVATION OF FES TYROSINE KINASE BY GP130, AN INTERLEUKIN-6 FAMILY CYTOKINE SIGNAL TRANSDUCER, AND THEIR ASSOCIATION
T MATSUDA; T FUKADA; M TAKAHASHITEZUKA; Y OKUYAMA; Y FUJITANI; Y HANAZONO; H HIRAI; T HIRANO, JOURNAL OF BIOLOGICAL CHEMISTRY, 270, 19, 11037, 11039, May 1995
English, Introduction scientific journal - ASSOCIATION AND ACTIVATION OF BTK AND TEC TYROSINE KINASES BY GP130, A SIGNAL TRANSDUCER OF THE INTERLEUKIN-6 FAMILY OF CYTOKINES
T MATSUDA; M TAKAHASHITEZUKA; T FUKADA; Y OKUYAMA; Y FUJITANI; S TSUKADA; H MANE; H HIRAI; ON WITTE; T HIRANO, BLOOD, 85, 3, 627, 633, Feb. 1995, ［Internationally co-authored］, [International Magazine]
English, Introduction scientific journal - サイトカインとそのレセプター インターロイキン6(IL-6)
臨床免疫, 27(Suppl. 16), 64-72, 1995 - Signal transduction through IL-6 receptor: Involvement of multiple protein kinases, stat factors, and a novel H7-sensitive pathway
K Nakajima; T Matsuda; Y Fujitani; H Kojima; Y Yamanaka; K Nakae; T Takeda; T Hirano, INTERLEUKIN-6 TYPE CYTOKINES, 762, 55, 70, 1995
English - ESTABLISHMENT OF THE ELISA FOR MURINE SOLUBLE GP130, A SIGNAL TRANSDUCER FOR THE IL-6 FAMILY CYTOKINE, AND ITS DETECTION IN THE ASCITIC FLUIDS OF TUMOR-BEARING MICE
T MATSUDA; T HIRANO, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 202, 1, 637, 642, Jul. 1994
English - SIGNAL-TRANSDUCTION THROUGH GP130 THAT IS SHARED AMONG THE RECEPTORS FOR THE INTERLEUKIN-6 RELATED CYTOKINE SUBFAMILY
T HIRANO; T MATSUDA; K NAKAJIMA, STEM CELLS, 12, 3, 262, 277, May 1994
English, Book review - INTERLEUKIN-6-INDUCED TYROSINE PHOSPHORYLATION OF MULTIPLE PROTEINS IN MURINE HEMATOPOIETIC LINEAGE CELLS
T MATSUDA; Y YAMANAKA; T HIRANO, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 200, 2, 821, 828, Apr. 1994
English - シグナル伝達機構の人為的再構築と修飾
免疫薬理, 12(4), 446-452, 1994 - Interleukin 6 receptor and signal transduction, Advances in Cell and Molecular.
Biology of Membranes and Organelles., 3: 65-92, 1994 - Association of p72 tyrosine kinase with Stat factors and its activation by IL-3, IL-6 and G-CSF.
Blood, 83: 3457-3461, 1994 - Interleukin 6 receptor and signal transduction, Advances in Cell and Molecular.
Biology of Membranes and Organelles., 3: 65-92, 1994 - Association of p72 tyrosine kinase with Stat factors and its activation by IL-3, IL-6 and G-CSF.
Blood, 83: 3457-3461, 1994 - URINARY LEVELS OF IL-6 IN PATIENTS WITH ACTIVE LUPUS NEPHRITIS
M IWANO; K DOHI; E HIRATA; N KURUMATANI; Y HORII; H SHIIKI; A FUKATSU; T MATSUDA; T HIRANO; T KISHIMOTO; H ISHIKAWA, CLINICAL NEPHROLOGY, 40, 1, 16, 21, Jul. 1993
English - インターロイキン6
外科と代謝・栄養, 27(5), 341-356, 1993 - インターロイキン6受容体に連鎖するチロシンキナーゼの解析
成人病の研究, 12, 3-4, 1993 - 脳神経系と免疫系をめぐるサイトカインシグナル
免疫薬理, 11(2), 125-136, 1993 - INTERLEUKIN-6 IN MYELOMA PLASMACYTOMA
S SUEMATSU; T MATSUSAKA; T MATSUDA; T HIRANO; T KISHIMOTO, INTERNATIONAL REVIEW OF EXPERIMENTAL PATHOLOGY, 34, 91, 98, 1993
English, Book review - ABNORMAL DISTRIBUTION OF IL-6 RECEPTOR IN AGED MRL/LPR MICE - ELEVATED EXPRESSION ON B-CELLS AND ABSENCE ON CD4+ CELLS
KOBAYASHI, I; T MATSUDA; T SAITO; K YASUKAWA; H KIKUTANI; T HIRANO; T TAGA; T KISHIMOTO, INTERNATIONAL IMMUNOLOGY, 4, 12, 1407, 1412, Dec. 1992
English - CHARACTERIZATION OF GROWTH INHIBITORY FACTORS FOR MOUSE MONOCYTIC LEUKEMIA-CELLS
T KASUKABE; J OKABEKADO; Y HONMA; M HOZUMI; T MATSUDA; T HIRANO, LEUKEMIA RESEARCH, 16, 2, 139, 144, Feb. 1992
English - Interleukin 6.
Encyclopedia of Immunology, 2: 917-919, 1992 - Interleukin 6.
Encyclopedia of Immunology, 2: 917-919, 1992 - Generation of plasmacytomas with the chromosomal translocation t(12;15) in interleukin 6 transgenic mice
Sachiko Suematsu; Taiji Matsusaka; Tadashi Matsuda; Shinsuke Ohno; Jun-Ichi Miyazaki; Ken-Ichi Yamamura; Toshio Hirano; Tadamitsu Kishimoto, Proceedings of the National Academy of Sciences of the United States of America, 89, 1, 232, 235, 1992
National Academy of Sciences, English - DISTRIBUTION OF INTERLEUKIN-6 IN NORMAL AND DISEASED HUMAN KIDNEY
A FUKATSU; S MATSUO; H TAMAI; N SAKAMOTO; T MATSUDA; T HIRANO, LABORATORY INVESTIGATION, 65, 1, 61, 66, Jul. 1991
English - Cytokine and hemopoietic factors.Interleukin.6.(IL-6).
FUJIBAYASHI MARI; MATSUDA TADASHI, 臨床検査, 35, 5, 481, 484, May 1991
Japanese - AGE-ASSOCIATED INCREASE IN INTERLEUKIN-6 IN MRL LPR MICE
B TANG; T MATSUDA; S AKIRA; N NAGATA; S IKEHARA; T HIRANO; T KISHIMOTO, INTERNATIONAL IMMUNOLOGY, 3, 3, 273, 278, Mar. 1991
English - Interleukin 6
現代医療, 23(11), 3077-3087, 1991 - インターロイキン6―ベッドサイドから分子生物学へ
侵襲と免疫, 1, 3-14, 1991 - サイトカインレセプターファミリー
治療学, 25, 1428-1529, 1991 - 脳と免疫ーサイトカインの関わり（Ⅱ）ー
ブレインサイエンス, 2: p607-611, 1991 - 脳と免疫ーサイトカインの関わり（Ⅰ）ー
ブレインサイエンス, 2: p491-495, 1991 - インターロイキン6（IL-6）
臨床検査, 35(5), 481-484, 1991 - インターロイキン6とそのレセプター
蛋白質・核酸・酵素, 36(7), 1184-1194, 1991 - IL-6と免疫応答
造血因子, 2(1), 14-24, 1991 - Special issue : from IL-6 to IL-11, SCF.1 IL-6 and immune response.
ORITANI KENJI; MATSUDA TADASHI; HIRANO TOSHIO, 造血因子, 2, 1, 14, 24, Jan. 1991
Japanese - IL-6 IS PRODUCED BY OSTEOBLASTS AND INDUCES BONE-RESORPTION
Y ISHIMI; C MIYAURA; CH JIN; T AKATSU; E ABE; Y NAKAMURA; A YAMAGUCHI; S YOSHIKI; T MATSUDA; T HIRANO; T KISHIMOTO; T SUDA, JOURNAL OF IMMUNOLOGY, 145, 10, 3297, 3303, Nov. 1990
English - PURIFICATION AND CHARACTERIZATION OF SOLUBLE HUMAN IL-6 RECEPTOR EXPRESSED IN CHO CELLS
K YASUKAWA; T SAITO; T FUKUNAGA; Y SEKIMORI; Y KOISHIHARA; H FUKUI; Y OHSUGI; T MATSUDA; H YAWATA; T HIRANO; T TAGA; T KISHIMOTO, JOURNAL OF BIOCHEMISTRY, 108, 4, 673, 676, Oct. 1990
English - Production of autoimmune diseases by the transfer of IL-6 transgenic bone marrow.
松阪泰二; 末松佐知子; 審良静男; 松田正; 平野俊夫; 青笹克之; 宮崎純一; 山村研一; 岸本忠三, 日本免疫学会総会・学術集会記録, 20, 154, Oct. 1990
Japanese - Structure and function of cytokine and receptor.11 Relevance between diversity of a function of IL-6 and disease.
MATSUDA TADASHI, 臨床科学, 26, 9, 1115, 1122, Sep. 1990
Japanese - Interleukin-6(IL-6/BSF-2).
MATSUDA TADASHI; HIRANO TOSHIO, 日本臨床, 48, ’90 Zokan Jo Rinsho Meneki, 292, 297, 11 Jul. 1990
Japanese - PRODUCTION OF INTERLEUKIN-6 BY NORMAL HUMAN TROPHOBLAST
T KAMEDA; N MATSUZAKI; K SAWAI; T OKADA; F SAJI; T MATSUDA; T HIRANO; T KISHIMOTO; O TANIZAWA, PLACENTA, 11, 3, 205, 213, May 1990
English - Lymphokine determination methods. 7. Determination of interleukin-6 (IL-6).
MATSUDA TADASHI, Pure Chem Daiichi, 21, 1, 20, 24, Mar. 1990
Japanese - サイトカインレセプターとシグナル伝達
感染・炎症・免疫, 20(4), 257-275, 1990 - IL-6／IL-6受容体の構造と機能および異常発現と疾患との関わり
代謝, 27(10), 897-907, 1990 - サイトカインとレセプターの構造と機能IL-6の機能多様化と疾患とのかかわり
臨床科学, 26(9), 1115-1122, 1990 - サイトカイン各論 インターロイキン－6（IL-6/BSF-2）
日本臨床, 48(増刊 臨床免疫 上), 292-297, 1990 - インターロイキン6（IL-6）と自己免疫疾患
日本臨床, 48(増刊 臨床免疫 上), 785-790, 1990 - インターロイキン6産生腫瘍
BIO medica, 5(3), 258-261, 1990 - Interleukin 6 (IL-6).
Biotherapy, 2: 363-373, 1990 - Interleukin 6 (IL-6).
Biotherapy, 2: 363-373, 1990 - INTERLEUKIN-6 AND ITS RECEPTOR IN THE IMMUNE-RESPONSE AND HEMATOPOIESIS
T HIRANO; T TAGA; T MATSUDA; M HIBI; S SUEMATSU; B TANG; M MURAKAMI; T KISHIMOTO, INTERNATIONAL JOURNAL OF CELL CLONING, 8, 155, 167, Jan. 1990
English - Special issue. Anti-receptor antibodies and disorders. Autoimmune disorders and IL-6. For receptor treatment.
HIBI MASAHIKO; SUEMATSU SACHIKO; HIRATA YUICHI; MATSUDA TADASHI, 免疫薬理, 8, 1, 51, 58, Jan. 1990
Japanese - INVOLVEMENT OF IL-6 IN MESANGIAL PROLIFERATIVE GLOMERULONEPHRITIS
Y HORII; A MURAGUCHI; M IWANO; T MATSUDA; T HIRAYAMA; H YAMADA; Y FUJII; K DOHI; H ISHIKAWA; Y OHMOTO; K YOSHIZAKI; T HIRANO; T KISHIMOTO, JOURNAL OF IMMUNOLOGY, 143, 12, 3949, 3955, Dec. 1989
English - Introductory lectures to clinical aspects of allergy. 62. Interleukin 6 (IL-6). Part 2.
ISSHIKI HIROSHI; MATSUDA TADASHI, 月刊アレルギーの臨床, 114, 965, 967, Dec. 1989
Japanese - IGG1 PLASMACYTOSIS IN INTERLEUKIN-6 TRANSGENIC MICE
S SUEMATSU; T MATSUDA; K AOZASA; S AKIRA; N NAKANO; S OHNO; J MIYAZAKI; K YAMAMURA; T HIRANO; T KISHIMOTO, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 86, 19, 7547, 7551, Oct. 1989
English - IL-6 and its clinical aspects.
IWANO MASAYUKI; MATSUDA TADASHI; HORII YASUHIRO; HIRANO TOSHIO, Med Immunol, 18, 4, 568, 574, Oct. 1989
Japanese - Interleukin 6(IL-6). 1.
ISSHIKI HIROSHI; MATSUDA TADASHI, 月刊アレルギーの臨床, 112, 819, 822, Oct. 1989
Springer-Verlag, Japanese - Plasmacytosis in IL-6 transgenic mice.
末松佐知子; 松田正; 審良静男; 青笹克之; 中野直子; 宮崎純一; 山村研一; 平野俊夫; 岸本忠三, 日本免疫学会総会・学術集会記録, 19, 105, Oct. 1989
Japanese - PATHOGENIC SIGNIFICANCE OF INTERLEUKIN-6 (IL-6/BSF-2) IN CASTLEMANS DISEASE
K YOSHIZAKI; T MATSUDA; N NISHIMOTO; T KURITANI; L TAEHO; K AOZASA; T NAKAHATA; H KAWAI; H TAGOH; T KOMORI; S KISHIMOTO; T HIRANO; T KISHIMOTO, BLOOD, 74, 4, 1360, 1367, Sep. 1989
English - INTERLEUKIN-6 TRIGGERS THE ASSOCIATION OF ITS RECEPTOR WITH A POSSIBLE SIGNAL TRANSDUCER, GP130
T TAGA; M HIBI; Y HIRATA; K YAMASAKI; K YASUKAWA; T MATSUDA; T HIRANO; T KISHIMOTO, CELL, 58, 3, 573, 581, Aug. 1989
English - CONSTITUTIVE PRODUCTION OF INTERLEUKIN 6/B CELL STIMULATORY FACTOR-II FROM INFLAMMATORY SYNOVIUM
N MIYASAKA; K SATO; J HASHIMOTO; H KOHSAKA; K YAMAMOTO; M GOTO; K INOUE; T MATSUDA; T HIRANO; T KISHIMOTO; K NISHIOKA, CLINICAL IMMUNOLOGY AND IMMUNOPATHOLOGY, 52, 2, 238, 247, Aug. 1989
English - HUMAN INTERLEUKIN-6 AND TUMOR NECROSIS FACTOR-ALPHA PRODUCTION STUDIED AT A SINGLE-CELL LEVEL
U ANDERSSON; T MATSUDA, EUROPEAN JOURNAL OF IMMUNOLOGY, 19, 6, 1157, 1160, Jun. 1989
English, Introduction scientific journal - IL-6 BSF2 IN NORMAL AND ABNORMAL REGULATION OF IMMUNE-RESPONSES
T MATSUDA; S SUEMATSU; M KAWANO; K YOSHIZAKI; B TANG; O TANABE; T NAKAJIMA; S AKIRA; T HIRANO; T KISHIMOTO, ANNALS OF THE NEW YORK ACADEMY OF SCIENCES, 557, 466, 477, Jun. 1989
English - MOLECULAR-CLONING OF THE CDNAS FOR INTERLEUKIN-6 B-CELL STIMULATORY FACTOR-II AND ITS RECEPTOR
T HIRANO; T TAGA; K YAMASAKI; T MATSUDA; K YASUKAWA; Y HIRATA; H YAWATA; O TANABE; S AKIRA; T KISHIMOTO, ANNALS OF THE NEW YORK ACADEMY OF SCIENCES, 557, 167, 180, Jun. 1989
English - PRODUCTION OF INTERLEUKIN-6 AND ITS RELATION TO THE MACROPHAGE DIFFERENTIATION OF MOUSE MYELOID-LEUKEMIA CELLS (M1) TREATED WITH DIFFERENTIATION-INDUCING FACTOR AND 1-ALPHA,25-DIHYDROXYVITAMIN-D3
C MIYAURA; CH JIN; Y YAMAGUCHI; M TOMIDA; M HOZUMI; T MATSUDA; T HIRANO; T KISHIMOTO; T SUDA, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 158, 3, 660, 666, Feb. 1989
English - インターロイキン6（IL-6）
内科, 63(6), 1193-1194, 1989 - インターロイキン6
BIOTHERAPY, 3(6), 1472-1486, 1989 - サイトカインと自己免疫疾患 特にインターロイキン6を例として
細胞工学, 8(11), 949-957, 1989 - 脳と免疫 生化学的立場から
代謝, 26(臨時増刊), 45-54, 1989 - IL-6の構造と機能
Medical Immunology, 17(1), 6-8, 1989 - IL-6の構造・機能・レセプター
実験医学, 7(1), 13-20, 1989 - インターロイキン6（その2）
アレルギーの臨床, 9(13), 965-967, 1989 - インターロイキン6（その1）
アレルギーの臨床, 9(11), 819-822, 1989 - B細胞刺激因子
MEDICO, 21(1), 23-28, 1989 - Current concepts of b cell modulation
Tadashi Matsuda; Katsuhiko Yamasaki; Tetsuya Taga; Toshio Hirano; Tadamitsu Kishimoto, International Reviews of Immunology, 5, 2, 97, 109, 1989
Informa Healthcare, English - Interleukin 6 and its receptor: Pathological role in autoimmunity and lymphoid malignancy.
Advances in Immunopharmacology, 4: 161-168, 1989 - A MULTIFUNCTIONAL CYTOKINE (IL-6 BSF-2) AND ITS RECEPTOR
T HIRANO; T TAGA; K YAMASAKI; T MATSUDA; B TANG; A MURAGUCHI; Y HORII; S SUEMATSU; Y HIRATA; H YAWATA; M SHIMIZU; M KAWANO; T KISHIMOTO, INTERNATIONAL ARCHIVES OF ALLERGY AND APPLIED IMMUNOLOGY, 88, 1-2, 29, 33, Jan. 1989
English - IgGl plasmacytosis in interleukin 6 transgenic mice.
Proc. Natl. Acad. Sci. USA., 86: 7547-7551, 1989 - Interleukin 6 and its receptor: Pathological role in autoimmunity and lymphoid malignancy.
Advances in Immunopharmacology, 4: 161-168, 1989 - IDENTIFICATION OF ALPHA-2-MACROGLOBULIN AS A CARRIER PROTEIN FOR IL-6
T MATSUDA; T HIRANO; S NAGASAWA; T KISHIMOTO, JOURNAL OF IMMUNOLOGY, 142, 1, 148, 152, Jan. 1989
English - Interleukin-6. Structure, functions and receptors of IL-6.
MATSUDA TADASHI; TAGA TETSUYA; YAMASAKI KATSUHIKO, 実験医学, 7, 1, 13, 20, Jan. 1989
Japanese - EXCESSIVE PRODUCTION OF INTERLEUKIN-6/B CELL STIMULATORY FACTOR-II IN RHEUMATOID-ARTHRITIS
T HIRANO; T MATSUDA; M TURNER; N MIYASAKA; G BUCHAN; B TANG; K SATO; M SHIMIZU; R MAINI; M FELDMAN; T KISHIMOTO, EUROPEAN JOURNAL OF IMMUNOLOGY, 18, 11, 1797, 1801, Nov. 1988, ［Internationally co-authored］, [International Magazine]
English - INTERLEUKIN-6 (B-CELL STIMULATORY FACTOR 2)-DEPENDENT GROWTH OF A LENNERT LYMPHOMA-DERIVED T-CELL LINE (KT-3)
S SHIMIZU; T HIRANO; R YOSHIOKA; S SUGAI; T MATSUDA; T TAGA; T KISHIMOTO; S KONDA, BLOOD, 72, 5, 1826, 1828, Nov. 1988
English - IL-6 BSF-2 FUNCTIONS AS A KILLER HELPER FACTOR IN THE INVITRO INDUCTION OF CYTO-TOXIC T-CELLS
M OKADA; M KITAHARA; S KISHIMOTO; T MATSUDA; T HIRANO; T KISHIMOTO, JOURNAL OF IMMUNOLOGY, 141, 5, 1543, 1549, Sep. 1988
English - REGULATION OF BSF-2 IL-6 PRODUCTION BY HUMAN MONONUCLEAR-CELLS - MACROPHAGE-DEPENDENT SYNTHESIS OF BSF-2 IL-6 BY T-CELLS
Y HORII; A MURAGUCHI; S SUEMATSU; T MATSUDA; K YOSHIZAKI; T HIRANO; T KISHIMOTO, JOURNAL OF IMMUNOLOGY, 141, 5, 1529, 1535, Sep. 1988
English - Monoclonal antibody. 2. Techniques for making monoclonal antibody. 6. Effective techniques for making hybridoma using IL-6.
MATSUDA TADASHI; HIRANO TOSHIO, 実験医学, 6, 10, 920, 924, Sep. 1988
Japanese - INDUCTION OF NEURONAL DIFFERENTIATION IN PC12 CELLS BY B-CELL STIMULATORY FACTOR-II INTERLEUKIN-6
T SATOH; S NAKAMURA; T TAGA; T MATSUDA; T HIRANO; T KISHIMOTO; Y KAZIRO, MOLECULAR AND CELLULAR BIOLOGY, 8, 8, 3546, 3549, Aug. 1988
English, Introduction scientific journal - Pleiotropic functions of BSF-2/IL-6.
MATSUDA TADASHI; HIRANO TOSHIO, 蛋白質 核酸 酵素, 33, 8, 1317, 1322, Jul. 1988
共立出版, Japanese - ESTABLISHMENT OF AN INTERLEUKIN 6 (IL 6)/B-CELL STIMULATORY FACTOR 2-DEPENDENT CELL-LINE AND PREPARATION OF ANTI-IL-6 MONOCLONAL-ANTIBODIES
T MATSUDA; T HIRANO; T KISHIMOTO, EUROPEAN JOURNAL OF IMMUNOLOGY, 18, 6, 951, 956, Jun. 1988
English - Functional diversity and abnormal expression of BSF-2/IL-6.
HIRANO TOSHIO; TAGA TETSUYA; MATSUDA TADASHI; HORII YASUHIRO; TANG B; KAWANISHI YOSHIKAZU; SUEMATSU SACHIKO; KISHIMOTO TADAMITSU, 日本臨床, 46, 5, 1029, 1035, May 1988
Japanese - INTERLEUKIN-6 (BSF2/IL-6) IS AN AUTOCRINE GROWTH-FACTOR FOR HUMAN MULTIPLE MYELOMAS
M KAWANO; T HIRANO; T MATSUDA; T TAGA; Y HORII; K IWATO; H ASAOKU; B TANG; O TANABE; H TANAKA; A KURAMOTO; T KISHIMOTO, PROCEEDINGS OF THE JAPAN ACADEMY SERIES B-PHYSICAL AND BIOLOGICAL SCIENCES, 64, 3, 68, 71, Mar. 1988
English - AUTOCRINE GENERATION AND REQUIREMENT OF BSF-2/IL-6 FOR HUMAN MULTIPLE MYELOMAS
M KAWANO; T HIRANO; T MATSUDA; T TAGA; Y HORII; K IWATO; H ASAOKU; B TANG; O TANABE; H TANAKA; A KURAMOTO; T KISHIMOTO, NATURE, 332, 6159, 83, 85, Mar. 1988
English - THE ESSENTIAL ROLE OF B-CELL STIMULATORY FACTOR-II (BSF-2/IL-6) FOR THE TERMINAL DIFFERENTIATION OF B-CELLS
A MURAGUCHI; T HIRANO; B TANG; T MATSUDA; Y HORII; K NAKAJIMA; T KISHIMOTO, JOURNAL OF EXPERIMENTAL MEDICINE, 167, 2, 332, 344, Feb. 1988
English - インターロイキン6とそのレセプター
代謝, 25(9), 859-869, 1988 - IL-6とリウマチ疾患
生体防御, 5(2), 211-216, 1988 - BSF-2／IL-6の生物学的機能の多様性
蛋白質・核酸・酵素, 33(8), 1317-1322, 1988 - BSF-2／IL-6の機能多様性と異常発現
日本臨床, 46(5), 1029-1035, 1988 - 〔自己免疫病 基礎･臨床研究の新しい動向〕B細胞刺激因子（BSF-2）と自己免疫疾患
日本臨床, 46(4), 749-754, 1988 - IL-6を用いた効率的ハイブリドーマ作成法
実験医学増刊, 6(10), 66-71, 1988 - B細胞の増殖・分化因子とその異常
癌・免疫・栄養, 2(4), 1-5, 1988 - ABSENCE OF ANTIVIRAL ACTIVITY IN RECOMBINANT B-CELL STIMULATORY FACTOR-II (BSF-2)
T HIRANO; T MATSUDA; K HOSOI; A OKANO; H MATSUI; T KISHIMOTO, IMMUNOLOGY LETTERS, 17, 1, 41, 45, Jan. 1988
English - STRUCTURE AND EXPRESSION OF HUMAN B-CELL STIMULATORY FACTOR-II (BSF-2/IL-6) GENE
K YASUKAWA; T HIRANO; Y WATANABE; K MURATANI; T MATSUDA; S NAKAI; T KISHIMOTO, EMBO JOURNAL, 6, 10, 2939, 2945, Oct. 1987
English - B細胞刺激因子とB細胞の分化
Medical Immunology, 14(5), 645-651, 1987 - COMPLEMENTARY-DNA FOR A NOVEL HUMAN INTERLEUKIN (BSF-2) THAT INDUCES LYMPHOCYTES-B TO PRODUCE IMMUNOGLOBULIN
T HIRANO; K YASUKAWA; H HARADA; T TAGA; Y WATANABE; T MATSUDA; S KASHIWAMURA; K NAKAJIMA; K KOYAMA; A IWAMATSU; S TSUNASAWA; F SAKIYAMA; H MATSUI; Y TAKAHARA; T TANIGUCHI; T KISHIMOTO, NATURE, 324, 6092, 73, 76, Nov. 1986
English - LIMITED PROTEOLYSIS OF A CHEMICALLY MODIFIED 3RD COMPONENT OF HUMAN-COMPLEMENT, C-3, BY CATHEPSIN-G OF HUMAN-LEUKOCYTES
T MATSUDA; S NAGASAWA; T KOIDE; J KOYAMA, JOURNAL OF BIOCHEMISTRY, 98, 1, 229, 236, 1985
English - LOCATION OF THE INTER-CHAIN DISULFIDE BONDS OF THE 3RD COMPONENT OF HUMAN-COMPLEMENT
T MATSUDA; T SEYA; S NAGASAWA, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 127, 1, 264, 269, 1985
English
- Interleukin-6 (IL-6).
Cytokine Reference Academic Press., 2000 - Interleukin-6 (IL-6).
Cytokine Reference Academic Press., 2000 - IL-6の遺伝子発現機構
Annual Review免疫 1995, 1995 - GM-CSF受容体
広川タンパク質化学 第2巻 受容体タンパク質Ⅰ, 1993 - インターロイキン6受容体
広川タンパク質化学 第2巻 受容体タンパク質Ⅰ, 1993 - サイトカインレセプターとシグナル伝達
Annual Review 免疫 1992, 1992 - IL-6
サイトカイン療法 南江堂, 1992 - インターロイキン6
医学のあゆみ 別冊巻 サイトカイン 基礎から臨床応用まで, 1992 - B細胞の増殖・分化
免疫・炎症・膠原病 メデイカル葵出版, 1991 - IL-6とそのレセプター
Annual Review 細胞生物学 1991, 1991 - インターロイキン6(IL-6)の機能多様性とB細胞異常 改訂
がん遺伝子研究最近の進歩, 1991 - サイトカインと疾患
小児医学の進歩’91A 中山書店, 1991 - インターロイキン6
新生化学実験講座12 分子免疫学Ⅰ 東京化学同人, 1989 - 増殖分化因子遺伝子の単離
新生化学実験 講座 7 増殖分化因子とその受容体 東京化学同人, 1989 - Interleukin 6 and its receptor in immune regulation.
Progress in Immunology., 1989 - Interleukin-6 and its receptor.
Lymphokine Receptor Interations. Eds D. Fradelizi, J. Bertoglio. Colloque INSERM/John Libbey Eurotext Ltd., 1989 - Differentiation and regulation of immunocompetent cells: interleukin 6 in immune regulation.
Progress in Allergy and Clinical Immunology. Editors W. J. Pichler, B. M. Stadler, C. A. Dahinden, A. T. P'ecoud, P. Frei, C. H. Schneider, A. L.. de Weck. Hogrefe and Huber Publeshers, Toronto., 1989 - Normal and abnormal regulation of human B cell differentiation by a new cytokine, BSF-2/IL-6.
Mechanisms of Lymphocyte Activation and Immune Regulation, vol 2 edited by S. Gupta, and W. E. Paul., Plenum Publishing Corporation., 1989 - Interleukin 6 and its receptor.
Proceedings of the Mochida Memorial Symposium on Recent Progress in Cytokine Research. Modical View Co. Ltd, Tokyo,, 1989 - Interleukin 6 and its receptor in immune regulation.
Progress in Immunology., 1989 - Interleukin-6 and its receptor.
Lymphokine Receptor Interations. Eds D. Fradelizi, J. Bertoglio. Colloque INSERM/John Libbey Eurotext Ltd., 1989 - Differentiation and regulation of immunocompetent cells: interleukin 6 in immune regulation.
Progress in Allergy and Clinical Immunology. Editors W. J. Pichler, B. M. Stadler, C. A. Dahinden, A. T. P'ecoud, P. Frei, C. H. Schneider, A. L.. de Weck. Hogrefe and Huber Publeshers, Toronto., 1989 - Normal and abnormal regulation of human B cell differentiation by a new cytokine, BSF-2/IL-6.
Mechanisms of Lymphocyte Activation and Immune Regulation, vol 2 edited by S. Gupta, and W. E. Paul., Plenum Publishing Corporation., 1989 - Interleukin 6 and its receptor.
Proceedings of the Mochida Memorial Symposium on Recent Progress in Cytokine Research. Modical View Co. Ltd, Tokyo,, 1989 - A new cytokine, BSF-2/IL-6 and its receptor.
B cell development, edited by O. N. Witte, N. Klinman and M C. Howard. Alan R. Liss Inc., New York., 1988 - A new cytokine, BSF-2/IL-6 and its receptor.
B cell development, edited by O. N. Witte, N. Klinman and M C. Howard. Alan R. Liss Inc., New York.., 1988 - Molecular structure and immunological function of human B cell differentiation factor (BSF2).
Molecular basis of lymphokine action, edited by D. R. Webb, C. W. Pierce, and S. Cohen, The Human Press Inc., 1987 - Molecular structure and immunological function of human B cell differentiation factor (BSF2).
Molecular basis of lymphokine action, edited by D. R. Webb, C. W. Pierce, and S. Cohen, The Human Press Inc., 1987
■ Research Themes
- ポストコロナの感染症・がん予防に向けての貪食促進型赤血球ワクチンの創製
科学研究費助成事業
30 Jun. 2023 - 31 Mar. 2025
松田 正; 半田 悠; 室本 竜太; 鍛代 悠一
日本学術振興会, 挑戦的研究(萌芽), 北海道大学, 23K18170 - Study of signaling pathways for treatment of immune/allergic diseases
Grants-in-Aid for Scientific Research
01 Apr. 2019 - 31 Mar. 2022
Matsuda Tadashi
Cytokines control the proliferation and differentiation as well as effecter functions of immune cells to eliminate invasive pathogens; however, they sometimes involve in the onset and development of immune/allergic diseases. We identified new regulatory molecules in the cytkine signaling and analyzed their functions. Among them, we focused on STAT3 / NF-κB-related signals, which are important for controlling the function of cytokines responsible for immune / allergic responses. However, the details of the involvement of these molecules in the development of immune / allergic diseases are not yet clear. In this study, we further examined functions of these STAT3 / NF-κB-related signaling molecules and showed new mechanisms in the onset of diseases such as allergies / immune diseases.This study will provide clues toward development of novel drugs for immune/allergic diseases in the near future.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, 19H03364 - Design and synthesis of phosphatidylserine dimers with antitumor effect via the phagocytosis-inducing property
Grants-in-Aid for Scientific Research
01 Apr. 2013 - 31 Mar. 2015
SHUTO satoshi; FUKUDA Hayato; ASAI Akira; MATSUDA Tadashi
We designed and synthesized dimer derivatives of phosphatidylserine as phagocytosis inducer via exposure of phosphor-serine polar-head moieties on cell surface, which are potentially used in immune cancer therapy. We successfully synthesized these dimer derivatives. We demonstrated that the liposomes containing the synthesized dimer derivatives of phosphatidylserine actually exposed the phosphor-serine polar-head moieties on cell surface in the evaluation with tumor cells.
Japan Society for the Promotion of Science, Grant-in-Aid for Challenging Exploratory Research, Hokkaido University, 25670048 - Effects of environmental chemicals on Th17 cells differenciation via aryl hydrocarbon receptor
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (C)
01 Apr. 2012 - 31 Mar. 2015
KOJIMA HIROYUKI; TAKEUCHI Shinji; MUROMOTO Ryuta; MATSUDA Tadashi
The retinoic acid receptor-related orphan receptor (ROR) and aryl hydrocarbon receptor (AhR) are key regulators of helper T (Th)17 cell differentiation. However, it remains unclear whether environmental chemicals, including dioxins, affect Th17 cell functions. In this study, we examined the AhR activity of 200 environmental chemicals using DR-EcoScreen assay, and found that several pesticides and isoflavones enhanced AhR-mediated transcriptional activity. These compounds increased the expression of IL-17A mRNA without effecting ROR mRNA levels in mouse T lymphoma EL4 cells. On the other hand, these chemicals did not affect the IL-17A gene expression in ROR- or AhR-knockdown EL4 cells. Taken together, these results suggest that several AhR agonists might enhance IL-17 production via ROR and AhR. This study also provides the evidence that environmental chemicals can act as modulators of IL-17 gene expression in immune cells.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido Institute of Public Health, 24590773 - P.acnes由来肉芽腫形成因子の同定とワクチンへの応用
科学研究費助成事業 新学術領域研究(研究領域提案型)
01 Apr. 2012 - 31 Mar. 2014
松田 正
肉芽腫形成は自然炎症反応による病変のひとつであり、細菌感染など病原体の侵入に対して、病原体を隔離する生体防御のひとつと考えられている。興味深いことにシグナル伝達分子Tyk2欠損マウスにおいてP.acnes誘導性の肉芽腫形成反応が抑制されることを見出しており、Tyk2欠損マウスを利用しつつ、肉芽腫形成を担うP.acnes由来因子を同定し、その特異的モノクローナル抗体の獲得と、特異的モノクローナル抗体による肉芽腫形成の阻害、さらにP.acnes由来因子による肉芽腫形成の分子機構の解明するため本年度は以下の研究を行なった。1.肉芽腫形成応答におけるケモカイン群の解析 P.acnes誘導性の肉芽腫形成反応に対応して種々のサイトカインやケモカインの産生が誘導されるが、Tyk2KOマウスにおいてはそれらの産生低下が顕著である。特にP.acnesによりマクロファージにより誘導されるケモカイン群発現に注目し、その分子機構を検討し、Tyk2下流のSTAT3の活性化が重要であることが明らかとなっている。2. P.acnes菌体からのP.acnes由来肉芽腫形成因子の精製とP.acnes由来肉芽腫形成因子に対する抗体の作製 現在、P.acnes由来蛋白に対するポリクローナル、モノクローナル抗体を作成しており、それらの抗体を用いた肉芽腫形成や免疫活性化効果への影響を検討する予定である。3.活性型Tyk2変異体発現トランスジェニックマウスでのP.acnes誘導肉芽腫形成の解析 すでに種々のTyk2点変異体の作成により活性増強されたTyk2変異体を発見しており、より効率的P.acnes誘導性の肉芽腫形成反応検出のための活性型Tyk2Tgマウスを作製する予定である。さらにこれらの研究過程でTyk2が炎症応答を惹起するサイトカインIL-23による病気発症に重要であることも明らかにした（論文投稿中）。
日本学術振興会, 新学術領域研究(研究領域提案型), 北海道大学, 24117701 - 癌・免疫疾患発症とシグナル異常：STAT3とNFーκBを中心として
科学研究費助成事業 基盤研究(B)
01 Apr. 2011 - 31 Mar. 2014
松田 正; 室本 竜太; 今 重之; 関根 勇一; 南保 明日香
生体の恒常性の維持にはサイトカインの存在が不可欠であり、中でも炎症性サイトカイン、インターロイキン6(IL-6)の異常産生やシグナル異常は癌、自己免疫疾患の発症に深く関与している。申請者はIL-6のシグナル分子STAT3の活性化及び活性化制御に関与する多くの分子を同定し、機能解析を行ってきた。本研究ではSTAT3と炎症応答を制御するNF-kappaBとの機能的相互作用の解析を中心に生体内STAT3制御法の確立を目指し、本年度は以下の研究を行った。1.STAT3結合蛋白のSTAT3機能への影響解析 これまでSTAT3制御因子としてY14を同定したが、Y14がNF-kappaBの活性制御にも関与する新規機能分子であることを明らかにした（論文投稿中）。2.STAT3とNF-kappaBとのクロストークを指標にしたSTAT3制御機構の解析 これまで核内蛋白KAP1がSTAT3、NF-kappaB、p300等と相互作用し、TNF/NF-kappaB依存的な炎症性サイトカインIL-6の遺伝子発現を制御することを見い出し報告したが、今回STAT3によるNF-kappaB活性化調節にSTAT3のセリンリン酸化が関与することを明らかにした。3.STAT3結合蛋白の新規機能解析STAT3の活性化を制御するSTAT3結合蛋白STAP-2が免疫系T細胞の活性化細胞死やCML慢性骨髄性白血病の原因蛋白BCR-ABLの活性化に関与することも明らかにした。さらに植物性イソフラボンが免疫系細胞においてSTAT3の活性化を誘導し、炎症性サイトカイン産生を増強することも世界で初めて明らかにした。
日本学術振興会, 基盤研究(B), 北海道大学, 23390015 - 疾患関連シグナルにおける低分子量二重特異性ホスファターゼの機能解析
科学研究費助成事業 挑戦的萌芽研究
2009 - 2010
松田 正; 室本 竜太; 関根 勇一
近年の自己免疫疾患やがんの疾患発症の分子メカニズムの研究により明らかになり始めた『シグナル伝達系の制御』白群の代表であるプロテインホスファターゼのうち、近年その生理的機能の一部が明らかになり、注目されるユニー群、低分子量二重特異性ホスファターゼを中心に、ホスファターゼによる疾患関連シグナルの制御機構の解析を行っ
1.種々の組織・細胞株でのDUSP遺伝子発現とサトカイン、増殖因子、ステロイドホルモン等の各種シグナルによ誘導の解析
サイトカイン、ステロイドホルモン刺激による各種DUSPのmRNA発現の誘導をRT-PCRにより、評価し、それらの刺激に導されるDUSPを同定した。
2.疾患シグナルにおけるDUSP遺伝子ノックダウンによる影響を解析
申請者らが確立したサイトカイン、増殖因子、ステロイドホルモンレセプターシグナルをモニターしうるレポーター法を用いて、細胞株で種々のDUSP遺伝子をsiRNAノックダウンすることにより、当該DUSPのシグナルへの影響を評価し連サイトカインシグナルを正に制御するDUSPを同定し、現在論文投稿準備中である。
3.ホスファターゼによる転写活性化複合体の制御機構の解析
疾患シグナルを制御する転写活性化制御複合体の重要な構成蛋白であるKAP1が疾患関連シグナル伝達分子STAT3のリン酸化、脱リン酸化に影響することによって転写活性化制御を担うことを明かにし、現在論文投稿中である。
日本学術振興会, 挑戦的萌芽研究, 北海道大学, 21659014 - Activation and regulation of the disease-related IL-6/STAT3 signaling
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
2008 - 2010
MATSUDA Tadashi; MUROMOTO Ryuta; SEKINE Yuichi; OHBAYASHI Norihiko; NANBO Asuka
Since we cloned interleukin-6 (IL-6) as B cell stimulatory factor 2 in 1986, IL-6 has been reported to influence cell proliferation, differentiation, and survival as well as mature cell functions. Signal transducer and activator of transcription 3 (STAT3) is a key molecule to mediate IL-6-induced cellular events. Indeed, STAT3 is activated in many tumor tissues, and the dimmer of STAT3 promotes cellular transformation, indicating that STAT3 itself can act as a proto-oncogene. In addition to oncogenesis, IL-6/STAT3 axis influences host immune systems. For example, IL-6/STAT3 axis is involved in the Toll-like receptor signaling pathways, the development and maturation of dendritic cells, and the differentiation of Th17 T-cell subset. These facts are likely to suggest that manipulation of IL-6/STAT3 signals could be suitable target for a variety of disease such as cancer and autoimmune diseases. We have energetically examined regulatory mechanisms of IL-6/STAT3-mediated signal transduction for the development of novel therapeutic strategies.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, 20390017 - Molecular mechanisms of STAT3 activation and their therapeutic applications
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B)
2006 - 2007
MATSUDA Tadashi; OHBAYASHI Norihiko; SEKINE Yuichi
STAT3 protein is mainly activated by IL-6 family of cytokines, epidermal growth factor, and leptin. Like other members of STAT family, STAT3 is tyrosine-phosphorylated by Jak kinases, then forms a dimer and translocates into the nucleus to activate target genes. It has been shown that the activated STAT3 alone can mediate cellular transformation. We cloned IL-6 as B cell stimularory factor 2 in 1986, and found its multiple functions and the relationship with several autoimmune diseases and cancers. After these outstanding works, we have continued the research concerning the mechanisms of IL-6 signal transduction. Especially, we have focused on STAT3 molecule in the IL-6/STAT3-mediated signaling pathway and reported several molecules, which regulate STAT3 positively or negatively. We also identified novel STAT3 binding proteins by using yeast two-hybrid system. Among them, one is ZIPK, a Ser/Thr kinase which phosphorylates STAT3 directly. We have also reported other STAT3 regulators, STAP-2, Daxx and LMW-DSP2 (DUSP22). In our research, we expect that STAT3 regulators, which directly interact with STAT3, may have critical roles in the regulation of STAT3 activation. More detailed understanding of interactions between these molecules and STAT3 is therefore important as new information may provide novel therapeutic approaches for the pathological conditions, including cancer and autoimmune diseases.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, 18390017 - エピジェニック効果を指標とした新規臨床検査法の確立
科学研究費助成事業 萌芽研究
2006 - 2007
松田 正; 大林 典彦
免疫疾患や癌は、さらに増加傾向の一途を辿っている。加えて、その重症化も進み、日常生活に著しい支障を慢性的にきたすことから、国民の健康上重大な問題となっている。さらに患者のQOLの向上を図るためにも、疾患の状況を把握しうる確実なる診断法開発も必要である。本研究においては、近年の疾患発症の分子メカニズムの研究により明らかになり始めている核タンパク質のエピジェニック効果にスポットを当て、疾患における核タンパク質の異常なタンパク質修飾を特異的に、かつ迅速に検出しうる診断法の開発を目指すものである。実際、本研究において免疫疾患や癌等の疾患関連核タンパク質を標的としてその核タンパク質修飾を検出しうる測定系を樹立することにより、診断をより容易なものとし、最終的にはタンパク質修飾を標的とした特異的な治療薬開発を目指す。国民の保険医療において、安価で簡便な診断、副作用の少ない特異的治療薬の開発は医療費削減にも重要なポイントであ。本研究においては核タンパク質のエピジェニック効果に伴うタンパク質修飾を特異的に検出する抗体の作製により新規診断法の確立を行う。本年度はタンパク質のリン酸化部位あるいはアセチル化部位の同定とその特異的抗体の作成により、生体内での特異的修飾を検出できた。しかしながら抗体の力価さらにあげ、大量に産生しうるモノクローナル抗体の作成を進める必要があり、現在進めている。また、それを用いてのELISA測定法の予備実験にも成功しており、さらに産業化に向けて研究を進める。
日本学術振興会, 萌芽研究, 北海道大学, 18659036 - Supression of the expression of cyclooxygenase-2 by ozonides of oleate ester
Grants-in-Aid for Scientific Research
2004 - 2005
MIURA Toshiaki; MATSUDA Tadashi; TAMOTO Kouichi
Ozonized olive oil has been reported to exert anti-inflammatory effect. However, the details of chemical structure of ozonized olive oil and its action mechanism have long been unclear. We have recently demonstrated that the major component of the ozonized olive oil is triozonide of triolein. In this study, we identified several minor components of ozonized olive oil, including "cross ozonides" of low and high molecular weight. In addition, to elucidate the anti-inflammatory action mechanism of ozonized olive oil, we investigated the effects of ozonized olive oil and methyl oleate ozonides on the generation of PGE_2 and the expression of Cyclooxygenase-2 (COX-2) in Lipopolysaccharide (LPS)-stimulated macrophage-like THP-1 cells. Olive oil, methyl oleate and their ozonides did not affect cell viability and morphology within a concentration used. LPS-induced COX-2 expression and PGE_2 generation in macrophage-like THP-1 cells were not affected by olive oil itself. However, ozonized olive oil inhibited both reactions in a concentration-dependent manner. Methyl oleate ozonides also inhibited COX-2 expression and PGE_2 generation whereas oleic acid and methyl oleate did not show such inhibitory effects. Such actions of ozonized olive oil and methyl oleate ozonide were shown to be due to their inhibitory effect on lкB phosphorylation which is required for Nuclear factor-kappa B (NFкB) activation and subsequent COX-2 gene transcription in LPS-stimulated macrophages. The inhibitory effect was also observed with ozonide having no functional group except for ozonide ring. In addition, ozonized olive oil and methyl oleate ozonide showed no effect on the phosphorylations of p38 and JNK, which are involved in the activation of AP-1. These results demonstrate that ozonized olive oil and methyl oleate ozonides suppress LPS-induced PGE_2 generation in macrophage-like THP-1 cells through inhibition of COX-2 gene transcription by suppressing the lкBαNFкB pathway.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), HOKKAIDO UNIVERSITY, 16590080 - サイトカインのシグナル伝達
ライフサイエンス基礎科学研究
1995 - 2005
Competitive research funding - サイトカインシグナル伝達系におけるSTAT3制御蛋白の役割
科学研究費助成事業 特定領域研究
2004 - 2004
松田 正; 平 敬宏; 奈良 敏文
申請者らが世界に先駆けクローニングし、機能を明らかにしたIL-6の研究を元として、IL-6の下流のシグナル伝達分子STAT3結合蛋白を網羅的にクローニングし、解析を行なった。すでに申請者らはSTAT3の機能を修飾する蛋白としてステロイドレセプターやHSP90,チロシンホスファターゼTC-PTPに関する論文を報告し、IL-6/STAT3のシグナル伝達系の解析法を確立した。さらに最近STAT3に結合するアダプター蛋白STAP-2を同定し、そのノックアウトマウスにおいてLPS,IL-6刺激によるSTAT3の活性化、急性期蛋白誘導が抑制されることを明らかにした。また、このSTAP-2がSTAT5とも機能的相互作用することも明らかにした。
特に、本申請研究においてはSTAT3に特異的に結合するキナーゼとSTAT3の核移行に重要な新規トランスロケーターを同定し、その機能解析を行い、現在論文投稿中である。STAT3キナーゼはSTAT3のSer727をリン酸化し、STAT3の活性化を正に制御する。STAT3トランスロケーターはSTAT3の核移行に必須である。今後、STAT3キナーゼやトランスロケーター分子のSTAT3を介した自己免疫疾患の発症や細胞の癌化における役割を明らかにし、疾患におけるこのキナーゼ、トランスロケーターの生理的意義を明らかなものとする。
日本学術振興会, 特定領域研究, 北海道大学, 16043201 - The mechanism of granulopoiesis and leukemogenesis by the activation of Stat3
Grants-in-Aid for Scientific Research
2003 - 2004
SHIMODA Kazuya; MATSUDA Tadashi; HARADA Mine; NAGAFUJI Kouji; MIYAMOTO Toshihiro
The Jak-Stat pathway plays an essential role in cytokine signaling. G-CSF promotes granulopoiesis, and Stat3 is the principle Stat protein activated by G-CSF. Upon treatment with G-CSF, the IL-3 dependent cell line 32D clone 3(32Dcl3) differentiates into neutrophils, and 32Dcl3 cells expressing dominant-negative Stat3 (32Dcl3/DNStat3) proliferate in G-CSF without differentiation. Gene expression profile of G-CSF-stimulated cell lines revealed that the expression of C/EBP_α was up-regulated by the activation of Stat3. And activated Stat3 bound to C/EBP_α, leading to the enhancement of the transcription activity of C/EBP_α. Conditional expression of C/EBP_α in 32Dcl3/DNStat3 cells after G-CSF stimulation abolishes the G-CSF dependent cell proliferation and induces granulocytic differentiation. These results show that one of the major roles of Stat3 in G-CSF signaling pathway is to augment the function of C/EBP_α.
The function of Stat3 in vivo was examined using the Stat3 conditional deficient mice. Mice deficient for Stat3 in hematopoietic cells show neutrocytosis, and G-CSF-induced proliferation of progenitor cells was observed in Stat3-deficient mice. In hematopoietic cells from Stat3-deficient mice, trace levels of SOCS3, a negative regulator of granulopoiesis, were observed, and SOCS3 expression was not induced by G-CSF stimulation. Stat3 null bone marrow cells displayed a significant activation of ERK1/2 under basal conditions, and it was enhanced and sustained by G-CSF stimulation. Furthermore, the augmented proliferation of Stat3-deficient bone marrow cells in response to G-CSF was dramatically decreased by addition of a MEK1 inhibitor. Stat3 functions in vivo as a negative regulator of G-CSF signaling by inducing SOCS3 expression, and ERK activation is the major factor responsible for inducing the proliferation of hematopoietic cells in response to G-CSF.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), KYUSHU UNIVERSITY, 15390302 - 環境ホルモンによるステロイド、サイトカインおよび増殖因子のクロストークへの影響
科学研究費助成事業 特定領域研究
2002 - 2003
松田 正
本研究ではヒト胎性腎癌細胞株293T細胞にエストロゲンレセプターやそのレポーター遺伝子を導入することによってエストロゲンレセプターシグナルモデル系を、さらにサイトカインのシグナル伝達分子STATあるいはTGF-βの活性をモニターしうるレポーター遺伝子を導入することによってサイトカインあるいは増殖因子のシグナルモデルを再構築した。エストロゲンレセプターの活性化は17β-エストラジオール(E2)によりSTAT (STAT3)の活性化は293T細胞をIL-6やLIF (Leukemia inhibitory factor)で刺激することにより行ない、Smadの活性化は活性化タイプI型TGF-βレセプターを発現させることにより行なった。これらの刺激を組み合わせることによって互いのクロストークを観察することにより、エストロゲンレセプターがSTAT3と相互作用し、IL-6あるいはLIFの作用を抑制することを明らかにした。さらに増殖因子TGF-βやBMPのシグナル伝達分子であるSmad蛋白がエストロゲンレセプターと相互作用することにより、TGF-βやBMPの作用を制御し、エストゲンレセプター活性を増強することを293T細胞での再構築系やヒト乳癌細胞株MCF-7を用いて明らかにした。本研究においては、これらエストロゲンレセプターおよび増殖因子、サイトカインのシグナル伝達系を用いることにより、種々の環境ホルモンのこれらシグナル系への影響を検討した。エストロゲンレセプターを刺激するE2同様に種々の環境ホルモンによるエストロゲンレセプターの活性化は増殖因子TGF-βの刺激、すなわちTGF-βレセプターの活性化によって増強された。すなわち環境ホルモンもE2同様に増殖因子のシグナル伝達系とクロストークすることが観察された。また、E2によって増殖因子、サイトカインのシグナル系が抑制されることを明らかにしたが、検討した環境ホルモンのなかにはサイトカインによるSTAT3の活性化を逆に増強するものが存在した。その増強効果はドミナントネガテイブSTAT3やアンチエストロゲン、タモキシフェンによって抑制が認められた。また、増強効果を示す環境ホルモンによってMAPキナーゼの活性増強も観察された。
日本学術振興会, 特定領域研究, 北海道大学, 14042216 - TNFファミリー分子及びサイトカインを介するアポトーシス増殖シグナル伝達機構解明
科学研究費助成事業 特定領域研究
2002 - 2002
宮崎 忠昭; 松田 正
(1)細胞接着を阻害し、integrin receptor等の接着分子からのシグナルを抑制することにより、アポトーシス(接着依存性アポトーシス:anoikis)が誘導される。癌細胞の増殖および転移においてanoikisのメカニズムを解明することは癌治療のために重要であり、我々はこのanoikis誘導の機構においてDAP3 (death associated protein 3)が機能を有していることを見い出した。さらにこのDAP3の機能の制御はそのリン酸化によって行われていることを確認し、そのリン酸化を行うkinaseについても同定と解析を行った。
(2)癌の発症、増殖および浸潤とDAP3との関連性を検討するため、胃癌患者の癌組織部においてDAP3の発現をwestern blottingおよび組織切片の免疫染色を行って検討した。その結果、胃癌の中では印環細胞癌、低分化腺癌、腺扁平上皮癌においてDAP3の発現が著しく亢進している例を認めたため、現在、その発現が亢進しているDAP3のアミノ酸変異の有無について解析を行っている。また、胃癌患者由来の組織を用いて作成したcDNAを使用して、DAP3のシークエンスをPCRにより確認したところ、アミノ酸置換が考えられるDNAの変異を確認した。
(3)新たなアポトーシスを誘導する分子としてクローニングされたDeath Receptor 6 (DR6)のシグナル伝達機構を解明するため、DR6の細胞内領域に物理的に会合する分子を酵母two hybrid法によりスクリーニングした結果、その候補として18個の遺伝子産物をクローニングした。これらのうちクローニングされた頻度の高かった2個の遺伝子産物について哺乳類細胞内での会合を検討した結果、DR6との会合を確認した。
(4)TDAG8 (T cell death associated gene 8)遺伝子の発現誘導は、グルココルチコイドによる胸腺細胞株のアポトーシス誘導と相関していた。TDAG8のトランスジェニックマウスを作製し解析した結果、TDAG8はcaspaseの活性化に関与していることが明らかとなった。
日本学術振興会, 特定領域研究, 北海道大学, 14028002 - Tyk2ノックアウトマウスを用いたIL-12のシグナル伝達の解析
科学研究費助成事業
2001 - 2001
松田 正; 下田 和哉
サイトカインのシグナル伝達におけるJakファミリーキナーゼの重要性は十分理解されているが、その中でTyk2キナーゼは、当初IFNαのシグナル伝達に必須のキナーゼとして同定された。In vivoでのTyk2の役割を明確にするために我々はTyk2欠損マウスを作成し、Tyk2はIFNαの大部分のシグナル伝達に必須ではないことを明らかにした。さらにIFNα以外にその刺激によりTyk2を活性化する抗癌サイトカインとして知られるIL-12のシグナル伝達にTyk2が重要であることも示したが、今回さらにIL-12とならび生体内の抗癌作用に重要なlFNY誘導サイトカインであるIL-18についてTyk2欠損マウスを用いて検討した。IL-18は、Jak-STAT経路ではなく、NF-κBを介する経路でそのシグナルを伝達するが、Tyk2欠損マウス由来脾細胞では、野生型マウスと比べIL-12刺激時に約1/6、IL-18刺激時に約1/3とNK細胞活性が減少していた。また、IL-12,IL-18刺激によるT細胞の増殖にはTyk2の欠損は影響を与えなかったが、IL-12,IL-18刺激によるIFNγの産生は著明に低下していた。野生型マウスでIL-12刺激時にみられるT, NK細胞におけるIL-18レセプターの発現亢進が、Tyk2欠損マウス由来T, NK細胞では見られておらず、このことがJak-STAT経路ではなく、MAPキナーゼ、NF-κBを介する経路をシグナル伝達に用いるIL-18の作用がTyk2の欠損により傷害される機序の一つとして考えられる。
現在、これらサイトカインによる抗癌メカニズム解明に向けてTyk2ノックアウトマウス及び野生型マウス由来脾細胞をIL-12及びIL-18刺激により新たに誘導される遺伝子発現をMicroarray法により解析中であり、同定された新たな遺伝子の解析も進める予定である。
日本学術振興会, 特定領域研究(C), 富山医科薬科大学, 13214037 - ABNORMAL RECOMBINATION ACTIVATING GENE (RAG) AND IMMUNO DEFICIENCY
Grants-in-Aid for Scientific Research Grant-in-Aid for Scientific Research (B).
1999 - 2000
MURAGUCHI Atsushi; NAGATA Takuya; MATSUDA Tadashi; KISHI Hiroyuki
1. Human Rag genomic locus ; Using a fragment of human RAG-1 cDNA, we isolated genomic DNA clones that contained either first or second exon of human RAG-1. We determined its exon/intron organization and the transcriptional start site. Similarly, we isolated genomic DNA clones that contains first or second exon of human RAG-2 and determined its exon/intron structure and the transcription initiation site for RAG-2. These led us to reveal, for the first time, the organization of human genomic RAG-1 and RAG-2 locus.
2. Regulation of human RAG transcription ; We characterized promoter regions for human RAG-1 and RAG-2, and revealed that the 5' promoter region of RAG-lwas indispensable for its basal promoter activity. On the contrary, the sequences between -63 to -107 of RAG-2 were shown to be essential for its promoter acticity, suggesting the regulation of RAG-1 and RAG-2 transcription may be controled by different transcriptional mechanisms.
3. Regulation of murine RAG-2 ; We found that the regulation of the mouse RAG-2 promoter activity is confered to 80 nucleotide upstream of RAG-2. We also found that a B cell-specific transcription protein, Pax-5, and a T cell-specific transcription protein, GATA-3, bind to the -80 to -17 nt region in B cells and T cells, respectively. These results indicate that distinct DNA binding proteins, Pax-5 and GATA-3, may regulate the murine RAG-2 promoter in B and T lineage cells, respectively.
Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B)., TOYAMA MEDICAL AND PHARMACEUTICAL UNIVERSITY, 11470169 - 造血系構築とくにマクロファージ分化におけるIL-6シグナルの解析
科学研究費助成事業 重点領域研究
1994 - 1994
松田 正; 平野 俊夫
IL-6は造血系において、IL-6は、IL-3とともに多能性幹細胞コロニー形成を誘導し、巨核球に対してはその成熟化を誘導する。また、IL-6はマウスの骨髄性白血病細胞株M1のマクロファージへの分化を誘導する因子として注目されている。IL-6受容体は分子量80kDaのIL-6結合分子とそのシグナル伝達分子であるgp130により構成される。gp130分子の細胞内ドメインにはチロシンキナーゼ等のエフェクター分子に類似した構造は認められず、gp130分子を介するシグナル伝達系を明らかにするためにはgp130会合分子の同定は必須である。申請者らは非受容体型チロシンキナーゼであるJAKファミリーキナーゼならびにその下流に存在すると考えられるSTAT分子に注目し、それらに対する特異的抗体を用いた免疫沈降法にてIL-6刺激によるチロシンリン酸化の有無を検討した。JAKキナーゼ及びSTAT蛋白に対する抗体は合成ペプチドをウサギに免疫することにより得た。マウスgp130分子を高発現させたマウスプロB細胞株BAFm130細胞あるいはIL-6によってマクロファージへの分化が誘導されるY6細胞をIL-6と可溶性IL-6レセプターa鎖で刺激し、NP-40溶液で可溶化後、抗ホスホチロシン抗体あるいは抗JAK抗体、抗STAT抗体で免疫沈降したのち抗ホスホチロシン抗体によるウエスタンブロットを行った。BAFm130においたはgp130分子を刺激することにより種々の蛋白のチロシンリン酸化が誘導された(BBRC200:821,1994)。また、gp130刺激でJAKキナーゼとSTAT分子のチロシンリン酸化が観察された。さらに、JAKキナーゼは構成的にgp130分子に会合していることが明らかとなった。加えて、抗STAT抗体による免疫沈降物中には分子量72kDaの新たなチロシンキナーゼ(p72^)(p72STAT-associatcd tyrosinc kinasc)が含まれることを明らかにした。また、p72^ のチロシンキナーゼ活性はgp130刺激で上昇することを明らかにした(Blood83:3457,1994)。さらに、p72^ チロシンキナーゼのチロシンリン酸化はIL-6によってマクロファージへの分化が誘導されるY6細胞においてもチロシンリン酸化が誘導されることや他の造血系サイトカインであるIL-3やG-CSFによっても誘導されることから造血系サイトカインレセプター下流に共通に存在するチロシンキナーゼであると考えられる。現在、このp72^ のチロシンキナーゼの単離、精製を試みている。
日本学術振興会, 重点領域研究, 大阪大学, 06277211 - IL-6による発癌機構の解析
科学研究費助成事業
1993 - 1993
平野 俊夫; 松田 正; 中嶋 弘一
インターロイキン6(IL-6)受容体を介するシグナル伝達経路を明かにした。すなわち、初期応答遺伝子の一つであるjunB遺伝子のIL-6応答領域(JRE-IL6)に至るシグナル伝達経路には、Jakチロシンキナーゼと、未知の分子量7万のチロシンキナーゼが関与していることと、シグナル伝達性転写因子であるStatファミリー蛋白が関与していることを明かにした。Stat蛋白がDNA結合能を獲得するためには、チロシンキナーゼによるStat蛋白のチロシンリン酸化が必須である。さらに、H7感受性のプロセスがStat蛋白が転写活性を獲得するために必須であることを明かにした。このシグナル伝達経路は、Ras,Raf,Cキナーゼ,Ca/CM依存性キナーゼを使用しておらず、未知の経路であることを明かにした。さらにJRE-IL6活性化に至るシグナル伝達経路は、アデノウイルスのE1A蛋白によって抑制されること、この抑制は、E1AのCR1領域を含む部分が必要であることを明かにした。今後、IL-6で活性化される分子量7万のチロシンキナーゼの同定、及びH7感受性プロセスを明かにすると共に、E1A分子の標的分子を同定することによって、この新しいRas非依存性のシグナル伝達経路の全貌を明かにしたい。
日本学術振興会, がん特別研究, 大阪大学, 05152073 - 自己免疫疾患の発症機序に関する分子生物学的研究
科学研究費助成事業 一般研究(B)
1993 - 1993
平野 俊夫; 松田 正
慢性関節リウマチ(RA)患者の骨髄ストローマ細胞株を樹立し、正常人由来骨髄ストローマ細胞株と、プレB細胞増殖支持能を比較したところ、患者由来細胞株は、高い支持能を有していた。この支持能亢進は、未知の細胞膜分子によることを明らかにした。さらにこの未知の膜分子を同定するために、RA由来骨髄ストローマ細胞株に対するモノクローナル抗体、RF3を作製した。ひきつづきRF3が認識する膜蛋白(BST-1と命名)をコードするcDNAをクローニングした。BST-1はGPIアンカー型の新しい膜蛋白で、CD38と約30%のホモロジーを有していた。さらに、BALB3T3細胞に発現させることによって、プレB細胞に対する増殖支持能を示した。また、BST-1の染色体遺伝子は、第14番染色体のq32.3に位置していることを示した。BST-1分子は、RA由来骨髄ストローマ細胞株では、その発現が亢進していた。この事実は、RA骨髄には、なんらかの異常が存在し、その結果BST-1遺伝子の発現が亢進していると考えられる。IL-6の遺伝子異常発現の分子機序と共に、RAの原因を追及するための有用なアプローチとなると考えられる。
日本学術振興会, 一般研究(B), 大阪大学, 05454208 - IL-6による発癌機構の解析
科学研究費助成事業
1992 - 1992
平野 俊夫; 改正 恒康; 松田 正; 中嶋 弘一
1.IL-6シグナル伝達機構の解析
前年までに、IL-6によって誘導される初期応答遺伝子の一つであるJunB遺伝子プロモーターのIL-6応答領域(JRE-IL6)を決定し、JRE-IL6がEts結合部位とCREB/ATF結合領域を含んでいることを明かにした。本年度は、引き続きJRE-IL6活性化に至るIL-6シグナル伝達経路を詳細に解析した結果、このシグナル伝達経路には、C-キナーゼ、A-キナーゼ、Ras、Rafが全く関与せず未知のシグナル経路であることを明かにした。又、Ets結合部位に結合可能なDNA結合蛋白をコードするcDNA結合蛋白をコードするcDNAをIL-6反応細胞よりクローニングした。引き続き、このEts結合蛋白がIL-6シグナルによって実際に活性化されるか否かを検討中である。
2.IL-6受容体会合分子の解析
IL-6受容体は、分子量8万のα鎖と、シグナル伝達分子であるgp130によって構成されているが、我々は第三の分子が会合している可能性を示す結果を得た。引き続き、この第三分子の機能を解析中である。
3.IL-6遺伝子異常発現機構の解析
多発性骨髄腫患者より樹立した骨髄ストローマ細胞は、IL-6プロモーターをトランスに活性化しうる何らかの因子を有している。この因子をクローニングするためのモデル実験として、HTLV-1のTaxが実際にIL-6プロモーターをNF-κB結合部位を介して活性化することを明かにした。又、Tax遺伝子を100倍に希釈しても、IL-6プロモーター支配下のルシフェラーゼ遺伝子の発現が誘導されることを明かにした。現在、引き続きストローマ細胞由来トランスアクチベーター因子のクローニングを行っている。
日本学術振興会, がん特別研究, 大阪大学, 04152076 - Investigation of the molecular mechanisms of immunological disorders with abnormal expression of the interleukin 6 gene.
Grants-in-Aid for Scientific Research Grant-in-Aid for General Scientific Research (A)
1990 - 1992
HIRANO Toshio; KAISHO Tsuneyasu; MATSUDA Tadashi
To elucidate the molecular mechanism(s) of immunological disorders where abnormal expression of the interleukin 6(IL-6) gene is considered to play some roles, we first made a working hypothesis of the pathogenesis of autoimmune disease(s) such as rheumatoid arthritis (RA). We postulate the involvement of endogenous retrovirus and that virus-derived transactivator, such as HTLV-1 p40tax would induce the expression of a variety of genes including the IL-6 gene of which expression is essential for disease onset. On the basis of this hypothesis, we established the cloning system by which we can ultimately clone the cDNA encoding p40tax like molecule present in the synovial tissue of RA patient. We further demonstrated that HTLV-1 p40tax can induce IL-60 gene expression through NF-kB binding site. Furthermore, to develop efficient inhibitors of IL-6 actions, we investigated the IL-6 signal transduction. We identified a novel IL-6 responsive element of the junB gene (JRE-IL6) and demonstrated that the signalings activating the JRE-IL6 does not contain PKC,PKA,ras,and raf activation, demonstrating the presence of a novel signal transduction pathway.
Japan Society for the Promotion of Science, Grant-in-Aid for General Scientific Research (A), Osaka University, 02404032 - ILー6による発癌機構の解析
科学研究費助成事業
1990 - 1990
平野 俊夫; 改正 恒康; 松田 正; 中嶋 弘一
1.ILー6シグナル伝達機構の解析
ILー6によって誘導される初期応答遺伝子の一つであるjunB遺伝子プロモ-タ-のILー6応答領域を決定した。ILー6応答領域は、5'上流ー149〜ー125塩基対に位置し、ETS結合領域とCREB/ATF結合領域を含んでいることが明らかになった。ILー6応答には両部位の存在が必須であり、両結合部位に各々ETSファミリ-とCREB/ATFファミリ-に属するDNA結合蛋白が結合しうることを明らかにした。さらに、Etsー1,CREーBP1、及びjunBが協調的にILー6応答領域に作用しうることを直接証明した。
2.多発性骨髄腫ストロ-マ細胞の機能異常の解析
多発性骨髄腫の発症が骨髄ストロ-マ細胞の異常に基づく可能性を明らかにする目的で、患者より骨髄ストロ-マ細胞株を樹立した。B細胞前駆細胞の増殖支持能を検討したところ、正常骨髄由来ストロ-マ細胞と比較して、3〜10倍強い活性があることを明らかにした。又、この増殖支持能は、何らかの未知の接着因子によることを示した。
3.ILー6遺伝子異常発現機構の解析
多発性骨髄腫患者より樹立した骨髄ストロ-マ細胞に、ILー6プロモ-タ-とCATを結合した遺伝子を導入することにより、患者ストロ-マ細胞には、ILー6プロモ-タ-をトランスに活性化しうる何らかのトランスアクチベ-タ-が存在することを明らかにした。
日本学術振興会, がん特別研究, 大阪大学, 03152078 - 形質細胞腫/骨髄腫発生機構におけるインタ-ロイキン6とその受容体発現異常の解析
科学研究費助成事業 がん特別研究
1990 - 1990
平野 俊夫; 改正 恒康; 松田 正
我々は、インタ-ロイキン6(ILー6)遺伝子の異常発現がミエロ-マ形質細胞腫の発生に重要な役割を果たしていることを報告してきた。
C57BL/6(B6)マウスを使用して、ヒトILー6遺伝子を構成的に発現するトランスジェニックマウス(B6Tg)を作成したところ、著明な形質細胞の増加を認めることを以前に報告した。しかしながら、これらの形質細胞は、同系マウスに移植できなかった。
今回、プリスティンの投与にて形質細胞腫が容易に発生するBALB/cマウスとB6Tgの交配実験を行なったところ、t(12;15)のクロモゾ-ム転座を伴い、かつヌ-ドマウスに移植可能な形質細胞腫が発生することが明らかとなった。又免疫グロブリン遺伝子は、モノクロ-ナルな再構成パタ-ンを示していた。以上の事実より、ILー6遺伝子の異常発現とcーmyc遺伝子等の癌遺伝子の異常発現により、形質細胞腫が発生することが明かとなった。
本研究によって、少なくともマウスにおいては、ILー6遺伝子の異常発現によって、最終的に、形質細胞腫が発生しうること、又このためには、他の癌遺伝子の異常発現が必要であることが明かとなった。ILー6は、ヒトのミエロ-マ/形質細胞腫の増殖因子であり、臨床的に癌が増加する時期には、これら患者血清中にILー6が増加することが知られている。これらの事実は、ILー6遺伝子の異常発現がヒトミエロ-マ/形質細胞腫の発生にも重要な役割を演じていることを示唆している。今後解明されなければならない重要な問題は、ミエロ-マ患者におけるILー6遺伝子の異常発現を誘導している分子機構の解明であると考えられる。
日本学術振興会, がん特別研究, 大阪大学, 02152069 - 免疫異常症の病態および病因におけるIL-61BSF-2の免疫学的分子生物学的解析
科学研究費助成事業 奨励研究(A)
1989 - 1989
松田 正
日本学術振興会, 奨励研究(A), 大阪大学, 01790523
