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Hasebe Akira

Faculty of Dental Medicine　Division of Dental Medicine　Department of Pathobiological ScienceProfessor

　Prevotella intermediaなど歯周病原細菌はもちろん、口腔カンジダ症の主要な病原微生物であるCandida albicansが全身に及ぼす影響、またこれらの微生物が自然免疫系にどのように認識されるのかを中心に研究しています。また、臨床系の研究室とともに唾液細菌叢についての研究も進めており、興味深い結果が得られています。

　新たに、バクテリオファージに興味があるという大学院生が教室に入ってきたことをきっかけに、工学部の先生の協力のもとでファージ研究を開始しました。札幌市の下水から腸球菌に対するファージを分離し、その性状を調べる予定です。

Researcher basic information

■ Degree
  • 博士（歯学）, 北海道大学
■ URL
researchmap URLホームページURL■ Various IDs
J-Global ID■ Research Keywords and Fields
Research Keyword
  • Drug resistance
  • Inflammatory cytokines
  • Oral microbiota
  • Biofilm
  • Bacteriophage
  • Innate Immunity
  • Candida albicans
  • Periodontopathic bacteria
  • Prevotella intermedia
  • Bacteriology
  • Infectious Immunology
Research Field
  • Life Science, Bacteriology
■ Educational Organization

Career

■ Career
Committee Memberships
  • Jan. 2026 - Present
    日本細菌学会北海道支部, 支部会長, Society
  • Mar. 2020 - Present
    北海道歯学会, 理事
  • 2006 - Present
    日本マイコプラズマ学会, 評議員, Society
  • Apr. 2022 - Mar. 2024
    北海道歯学雑誌, 編集委員長, Society
  • Apr. 2021
    日本細菌学会 北海道支部, 評議員, Society
  • 2006 - 2021
    日本細菌学会, 北海道支部 幹事, Society

Research activity information

■ Awards
  • 2007, 第4回北海道歯学会賞
    Japan
■ Papers
  • Protein fractions associated with Prevotella intermedia suppress the growth of HSC-3 oral squamous cell carcinoma cells.
    Miyuki Kashiwabara; Machiko Kasai; Shintaro Nakano; Katsuki Takebe; Shiho Suzuki; Mariko Naito; Mikio Shoji; Ji-Won Lee; Tsukasa Akasaka; Yasuhiro Yoshida; Akira Hasebe; Yoichi Ohiro
    Journal of oral biosciences, 68, 5, 100803, 100803, 03 Aug. 2026, [Corresponding author], [International Magazine]
    English, Scientific journal, OBJECTIVES: Oral microbiomes are associated with the progression of oral squamous cell carcinoma (OSCC). Prevotella intermedia is associated with tumor progression; however, the direct effects of P. intermedia on OSCC cells have not been elucidated. In this study, the aim was to elucidate the direct effects of P. intermedia on OSCC cells. METHODS: HSC-2, HSC-3, and SAS cells were treated with P. intermedia OMA14 at multiplicities of infection of 10 and 100, and cell viability was then assessed using a cell-counting kit (CCK)-8 assay. The effects of heat-killed P. intermedia OMA14 and protein fractions prepared from SDS-PAGE-separated membrane strips on HSC-3 cell viability were assessed using the CCK-8 assay. Cell migration, cell cycle, and lactate dehydrogenase (LDH) cytotoxicity assays were performed using HSC-3 cells treated with P. intermedia OMA14. RESULTS: Treatment with P. intermedia OMA14 reduced HSC-3 cell viability, whereas there were no significant changes in SAS or HSC-2 cell viability. Heat-killed P. intermedia did not reduce HSC-3 cell viability. P. intermedia also suppressed HSC-3 cell migration, and it induced G0/G1-phase cell-cycle arrest without increasing LDH release. In addition, among the P. intermedia-derived protein fractions, the fractions corresponding to approximately 75 kDa and 15-20 kDa had the strongest inhibitory effects on HSC-3 cell viability. CONCLUSION: P. intermedia OMA14 reduced HSC-3 cell viability through an anti-proliferative mechanism associated with G0/G1-phase cell-cycle arrest rather than overt cytotoxicity. Protein fractions of approximately 75 kDa and 15-20 kDa showed the strongest inhibitory effects on HSC-3 cell viability.
  • Oral and Gut Microbiota in Individuals With Autism Spectrum Disorder: A Pilot Case–Control Study
    Airi Iida; Yuki Toyota; Tatsuki Itagaki; Yasutaka Yawaka; Akira Hasebe
    International Journal of Paediatric Dentistry, Wiley, 05 May 2026, [Peer-reviewed], [Last author]
    Scientific journal, ABSTRACT

    Background

    Recent studies suggest that gut microbiota play important roles in individuals with autism spectrum disorder (ASD), potentially influencing the development and severity of the condition. Oral bacteria may be directly or indirectly involved in the biological and symptomatic aspects of ASD through their effect on gut microbiota.

    Aim

    This pilot study aimed to characterise compositional alterations in the oral and gut microbiota of individuals with ASD and to identify bacterial taxa in saliva and faeces that may serve as potential microbial indicators of ASD.

    Design

    Salivary and faecal samples were collected from 10 individuals with ASD and 10 typically developing controls. The oral and gut microbiota were evaluated using 16S ribosomal RNA marker‐gene sequencing.

    Results and Conclusion

    Distinct features of the oral and gut microbiota were identified that differed between individuals with ASD and typically developing controls. Based on linear discriminant analysis effect size, the relative abundances of the genera Neisseria were higher in the oral microbiota of the ASD groups, whereas the genera Faecalibacterium were enriched in the gut microbiota. These findings highlight the potential relevance of the oral–gut–brain axis in ASD. Additionally, non‐invasive sampling of saliva and faeces may be utilised for early ASD screening.
  • Antiviral effect of cetylpyridinium chloride on SARS-CoV-2 in patients with COVID-19: An Observational Study.
    Ryo Takeda; Hirofumi Sawa; Michihito Sasaki; Yasuko Orba; Nako Maishi; Takuya Tsumita; Yoichi Ohiro; Akira Hasebe; Hidehiko Sano; Yoshimasa Kitagawa; Kyoko Hida; Yasuhiro Hida
    Journal of oral biosciences, 68, 2, 100772, 100772, Apr. 2026, [Peer-reviewed], [International Magazine]
    English, Scientific journal, OBJECTIVES: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the viral agent responsible for the COVID-19 pandemic and primarily invades the body through the oral cavity. Cetylpyridinium chloride (CPC), a widely used component of oral care products, has demonstrated antiviral effects against SARS-CoV-2; however, the clinical evidence remains limited. This study investigated the virucidal effects of oral CPC in patients with COVID-19 and its impact on reverse transcription polymerase chain reaction (RT-PCR) positivity. METHODS: Thirty-four patients with COVID-19 were initially recruited after obtaining positive PCR test result. This study was conducted during a nationwide Delta-variant-driven epidemic characterized by high viral loads and enhanced transmissibility. Saliva was collected at seven predefined time points to assess the effects of CPC-containing tablets and mouthwash. Viral RNA levels and infectious viral titers were quantified using qRT-PCR and plaque assays. Sixteen patients with detectable SARS-CoV-2 RNA in baseline saliva samples who completed all scheduled samplings constituted the final analytical cohort. RESULTS: During the Delta-variant-predominant period, CPC-containing tablets reduced both SARS-CoV-2 RNA levels and viral infectivity in saliva. In contrast, CPC-containing mouthwashes did not significantly reduce viral RNA levels compared to baseline samples. The RT-PCR positivity rates after CPC use varied according to the applied cycle threshold (Ct) cutoff values. CONCLUSIONS: CPC-containing tablets transiently decrease the SARS-CoV-2 salivary viral load and infectivity and may help reduce the risk of transmission in public settings. When CPC formulations are used prior to saliva-based PCR testing, the Ct cut-off values may require adjustment. CLINICAL SIGNIFICANCE: Despite challenges in conducting saliva-based clinical research in COVID-19 patients, this study provides clinical evidence supporting the antiviral efficacy of CPC formulations on salivary SARS-CoV-2 during the Delta-variant pandemic.
  • Materials informatics for glass ionomer cements: key features and design.
    Kenta Tsuchiya; Atsushi Tomokiyo; Lauren Takahashi; Salvatore Sauro; James Kit Hon Tsoi; Jukka P Matinlinna; Monica Yamauti; Akira Hasebe; Hidehiko Sano; Keisuke Takahashi
    Dental materials : official publication of the Academy of Dental Materials, 25 Feb. 2026, [Peer-reviewed], [International Magazine]
    English, Scientific journal, OBJECTIVES: The objective of this study was to investigate additive-dependent trends in the physicochemical properties of experimental glass ionomer cements (GICs), using an exploratory materials informatics framework as a data-analytical tool. METHODS: This study used a data-driven approach to analyze experimental GICs modified with fluoride-doped Ca-phosphates (FDCP) or Zn-polycarboxylate bioactive glass (BAG-Zn), compared with commercial Fuji™ IX GP (IX-GP) and Fuji™ II LC (II-LC). The independent variables were material type, particle type, and content (0-20 wt%). pH, ion release, and compressive strength were evaluated at 1, 7, and 28 days. Descriptive analysis and data visualization approaches such as pairwise correlation, parallel coordinate, and clustering analyses were applied to a previously published dataset. RESULTS: Pairwise correlation analyses revealed BAG-Zn increased both pH and F⁻ release, whereas FDCP reduced pH but enhanced Ca²⁺ release. The effects of additives varied with base materials-IX-GP tended to lower pH and raise Ca²⁺ release, while II-LC increased pH and compressive strength. Parallel coordinate analyses confirmed that additive type, base material, and mixing ratio were major contributing factors of ion release and strength. Clustering further identified 5-10 wt% BAG-Zn as the optimal composition, with FDCP maintaining favorable mechanical properties even at higher levels. SIGNIFICANCE: The present materials informatics approach enabled the identification of key variables and additive-dependent trends in experimental GICs. Even with a limited dataset, this exploratory framework provided structured, data-driven insights that may support future experimental design and systematic data expansion toward the development of improved GIC formulations.
  • Comment on Retuerto et al. Analysis of Gut Bacterial and Fungal Microbiota in Children with Autism Spectrum Disorder and Their Non-Autistic Siblings. Nutrients 2024, 16, 3004
    Tatsuki Itagaki; Ken-ichiro Sakata; Jun Sato; Akira Hasebe
    Nutrients, Nov. 2025
    Scientific journal
  • Induction of apoptotic cell death by calcitriol in RAW.264.7 cells
    Machiko Kasai; Shintaro Nakano; Keisuke Nakamura; Tsukasa Akasaka; Yasuhiro Yoshida; Shiho Suzuki; Ji-Won Lee; Yoshiaki Sato; Akira Hasebe.
    Hokkaido J Dent Sci, 46, 44, 53, Sep. 2025, [Peer-reviewed], [Last author, Corresponding author]
    English, Scientific journal
  • Selective Pyk2 inhibition enhances bone restoration through SCARA5-mediated bone marrow remodeling in ovariectomized mice.
    Yunqing Liu; Mai Nishiura; Mika Fujii; Sumiti Sandhu; Yasutaka Yawaka; Yutaka Yamazaki; Akira Hasebe; Tadahiro Iimura; Sek Won Kong; Ji-Won Lee
    Cell communication and signaling : CCS, 22, 1, 561, 561, 22 Nov. 2024, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Understanding the intricate cellular interactions involved in bone restoration is crucial for developing effective strategies to promote bone healing and mitigate conditions such as osteoporosis and fractures. Here, we provide compelling evidence supporting the anabolic effects of a pharmacological Pyk2 inhibitor (Pyk2-Inh) in promoting bone restoration. In vitro, Pyk2 signaling inhibition markedly enhances alkaline phosphatase (ALP) activity, a hallmark of osteoblast differentiation, through activation of canonical Wnt/β-catenin signaling. Notably, analysis of human mesenchymal stem cells through RNA-seq revealed a novel candidate, SCARA5, identified through Pyk2-Inh treatment. We demonstrate that Scara5 plays a crucial role in suppressing the differentiation from stromal cells into adipocytes, and accelerates lineage commitment to osteoblasts, establishing Scara5 as a negative regulator of bone formation. Additionally, Pyk2 inhibition significantly impedes osteoclast differentiation and bone resorption. In a co-culture system comprising osteoblasts and osteoclasts, Pyk2-Inh effectively suppressed osteoclast differentiation, accompanied by a substantial increase in the transcriptional expression of Tnfrsf11b and Csf1 in osteoblasts, highlighting a dual regulatory role in osteoblast-osteoclast crosstalk. In an ovariectomized mouse model of osteoporosis, oral administration of Pyk2-Inh significantly increased bone mass by simultaneously reducing bone resorption, promoting bone formation and decreasing bone marrow fat. These results suggest Pyk2 as a potential therapeutic target for both adipogenesis and osteogenesis in bone marrow. Our findings underscore the importance of Pyk2 signaling inhibition as a key regulator of bone remodeling, offering promising prospects for the development of novel osteoporosis therapies.
  • Comment on Dorobisz et al. Assessment of Prognostic Factors, Clinical Features Including the Microbiome, and Treatment Outcomes in Patients with Cancer of Unknown Primary Site. Cancers 2024, 16, 3416
    Tatsuki Itagaki; Machiko Kasai; ken-ichiro sakata; Akira Hasebe
    Cancers, Nov. 2024, [Peer-reviewed], [Last author]
    Scientific journal
  • Myths and misconceptions about microbiome analysis: Starting to Decode the Myths
    板垣, 竜樹; 長谷部, 晃
    Hokkaido journal of dental science, 45, 10, 11, 北海道歯学会, 15 Sep. 2024, [Last author]
    Japanese, Scientific journal
  • Enhanced phagocytosis associated with multinucleated microglia via Pyk2 inhibition in an acute β-amyloid infusion model
    Ji-Won Lee; Kaito Mizuno; Haruhisa Watanabe; In-Hee Lee; Takuya Tsumita; Kyoko Hida; Yasutaka Yawaka; Yoshimasa Kitagawa; Akira Hasebe; Tadahiro Iimura; Sek Won Kong
    Journal of Neuroinflammation, 21, 1, Springer Science and Business Media LLC, 06 Aug. 2024, [Peer-reviewed]
    Scientific journal
  • Compositional Data and Microbiota Analysis: Imagination and Reality
    Tatsuki Itagaki; Hirokazu Kobayashi; ken-ichiro sakata; Ikuya Miyamoto; Akira Hasebe; Yoshimasa Kitagawa
    Microorganisms, Jul. 2024, [Peer-reviewed], [Corresponding author]
    Scientific journal
  • Association between oral frailty and Prevotella percentage in the oral microbiota of community-dwelling older adults who participated in the CHEER Iwamizawa project, Japan.
    Chizuru Kimura; Kazuhito Miura; Yutaka Watanabe; Haruhisa Baba; Kimiya Ozaki; Akira Hasebe; Tokiyoshi Ayabe; Kiminori Nakamura; Shinji Nakaoka; Katsuhiko Ogasawara; Teppei Suzuki; Hiroshi Saito; Takashi Kimura; Akiko Tamakoshi; Yutaka Yamazaki
    Journal of oral rehabilitation, 08 Jun. 2024, [Peer-reviewed], [International Magazine]
    English, Scientific journal, BACKGROUND: Prevotella bacteria are associated with inherent diseases of the oral cavity, such as periodontal disease, and systemic diseases. Oral frailty (OF) has been associated with nursing necessity and death. However, the relationship between OF and oral microbiota has not been fully clarified. OBJECTIVE: This cross-sectional study investigated the association between OF and Prevotella percentage in the oral microbiota of community-dwelling older adults. METHODS: Oral bacteria species from saliva were identified in 208 community-dwelling older individuals aged ≥60 years in Japan. The proportion of Prevotella in the oral microbiota was classified into three tertile groups, and its relationship with each test item for OF (number of remaining teeth, masticatory performance, oral diadochokinesis, tongue pressure, difficulties eating tough foods, difficulties swallowing tea or soup, number of applicable OF judgement items, and existence of OF) was examined using ordinal logistic regression analysis. RESULTS: The Prevotella proportions were classified into lower, middle and upper groups, comprising 70, 69 and 69 participants, respectively. The three groups showed a significant relationship between the number of remaining teeth (odds ratio [OR]: 0.946, 95% confidence interval [CI]: 0.915-0.977), masticatory performance (OR: 0.897, 95% CI: 0.844-0.953), number of applicable OF judgement items (OR: 1.477, 95% CI: 1.14-1.915), and existence of OF (OR: 4.194, 95% CI: 1.519-11.576). CONCLUSION: The proportion of Prevotella in oral microbiota was high in individuals with OF. Among the older adults, the type of oral microbiota and systemic diseases may be related to the examination and management of oral function decline.
  • Epithelial-mesenchymal transition in oral cancer cells induced by prolonged and persistent Fusobacterium nucleatum stimulation
    Shintaro Nakano; Machiko Kasai; Keisuke Nakamura; Tsukasa Akasaka; Yasuhiro Yoshida; Shiho Suzuki; Yoichi Ohiro; Akira Hasebe
    Journal of Oral Biosciences, Elsevier BV, May 2024, [Peer-reviewed], [Corresponding author]
    Scientific journal
  • Oral bacterium Streptococcus mutans promotes tumor metastasis through thrombosis formation.
    Li Yu; Yuying Hong; Nako Maishi; Aya Yanagawa Matsuda; Yasuhiro Hida; Akira Hasebe; Yoshimasa Kitagawa; Kyoko Hida
    Cancer science, 14 Dec. 2023, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Thrombosis is a well-known cardiovascular disease (CVD) complication that has caused death in many patients with cancer. Oral bacteria have been reported to contribute to systemic diseases, including CVDs, and tumor metastasis. However, whether oral bacteria-induced thrombosis induces tumor metastasis remains poorly understood. In this study, the cariogenic oral bacterium Streptococcus mutans was used to examine thrombosis in vitro and in vivo. Investigation of tumor metastasis to the lungs was undertaken by intravenous S. mutans implantation using a murine breast cancer metastasis model. The results indicated that platelet activation, aggregation, and coagulation were significantly altered in S. mutans-stimulated endothelial cells (ECs), with elevated neutrophil migration, thereby inducing thrombosis formation. Streptococcus mutans stimulation significantly enhances platelet and tumor cell adhesion to the inflamed ECs. Furthermore, S. mutans-induced pulmonary thrombosis promotes breast cancer cell metastasis to the lungs in vivo, which can be reduced by using aspirin, an antiplatelet drug. Our findings indicate that oral bacteria promote tumor metastasis through thrombosis formation. Oral health management is important to prevent CVDs, tumor metastasis, and their associated death.
  • Exploratory Study of the Relationship between an Oral Fungal Swab Test and Patient Blood Test Data.
    Tatsuki Itagaki; Ken-Ichiro Sakata; Akira Hasebe; Yoshimasa Kitagawa
    Microorganisms, 11, 12, 29 Nov. 2023, [Corresponding author], [International Magazine]
    English, Scientific journal, Our understanding of the relationship between oral Candida and systemic conditions has significantly increased recently, which this study aims to extend further by investigating the risks of oral candidiasis. A total of 314 patients were involved in this study and underwent an oral swab test at the Department of Oral Medicine, Hokkaido University Hospital, between January and December 2021. Data were collected on age, sex, white and red blood cell counts, Hb, total protein, vitamin B12, as well as serum albumin, iron, copper, and zinc levels. The clinical fungus samples were swabbed to identify those with Candida species using a MALDI Biotyper, then applied analysis of covariance and multivariant logistic regression analysis. It was possible to assess the oral swab test results without considering the difference between sex (p = 0.946). The oral swab test results were associated with aging (odds ratio: 1.03) and serum albumin levels (odds ratio: 0.32). In summary, the results of our study suggest a relationship between aging and oral candidiasis and offer in-depth insights into how to prevent or treat oral candidiasis onset.
  • Genotypes and virulence-related activities of Candida albicans derived from oral cavity of patients in Hokkaido
    Chisato Ouchi; Akira Hasebe; Ken-ichiro Sakata; Jun Sato; Yutaka Yamazaki; Noritaka Ohga; Yoshimasa Kitagawa
    Archives of Oral Biology, 105827, 105827, Elsevier BV, Oct. 2023, [Peer-reviewed], [Corresponding author]
    Scientific journal
  • Development of Autopolymerizing Resin Material with Antimicrobial Properties Using Montmorillonite and Nanoporous Silica
    Shuhei Otsubo; Ko Nakanishi; Kakufu Fukukawa; Ryoshun Endo; Seiichiro Yoshida; Aiko Matsumoto; Kumiko Yoshihara; Tsukasa Akasaka; Akira Hasebe; Yasuhiro Yoshida; Yoshiaki Sato
    Pharmaceutics, 15, 2, 544, 544, MDPI AG, 06 Feb. 2023, [Peer-reviewed]
    Scientific journal, Although autopolymerizing resin offers numerous applications in orthodontic treatment, plaque tends to accumulate between the appliance and the mucosa, which increases the number of microorganisms present. In this study, we added cetylpyridinium chloride (CPC) loaded montmorillonite (Mont) and nanoporous silica (NPS) to autopolymerizing resin (resin-Mont, resin-NPS) and evaluated their drug release capacity, antimicrobial capacity, drug reuptake capacity, mechanical strength, and color tone for the devolvement of autopolymerizing resin with antimicrobial properties. As observed, resin-Mont and resin-NPS were capable of the sustained release of CPC for 14 d, and a higher amount of CPC was released compared to that of resin-CPC. Additionally, resin-Mont and resin-NPS could reuptake CPC. Moreover, the antimicrobial studies demonstrated that resin-Mont and resin-NPS could release effective amounts of CPC against Streptococcus mutans for 14 d and 7 d after reuptake, respectively. Compared to resin-CPC, resin-Mont exhibited a higher sustained release of CPC in all periods, both in the initial sustained release and after reuptake. However, the mechanical strength decreased with the addition of Mont and NPS, with a 36% reduction observed in flexural strength for resin-Mont and 25% for resin-NPS. The application of these results to the resin portion of the orthodontic appliances can prevent bacterial growth on the surface, as well as on the interior, of the appliances and mitigate the inflammation of the mucosa.
  • The oral bacterium Streptococcus mutans promotes tumor metastasis by inducing vascular inflammation
    Li Yu; Nako Maishi; Erika Akahori; Akira Hasebe; Ryo Takeda; Aya Yanagawa Matsuda; Yasuhiro Hida; Jin‐Min Nam; Yasuhito Onodera; Yoshimasa Kitagawa; Kyoko Hida
    Cancer Science, 1, 15, Wiley, 23 Aug. 2022, [Peer-reviewed]
    English, Scientific journal
  • Antibacterial potential of colloidal platinum nanoparticles against Streptococcus mutans.
    Hongbo Zhang; Akira Hasebe; Arefin Alam; Yunqing Liu; Shuhei Hoshika; Monica Yamauti; Hidehiko Sano
    Dental materials journal, 41, 3, 368, 375, 31 May 2022, [Peer-reviewed], [Corresponding author], [Domestic magazines]
    English, Scientific journal, This study evaluated the antibacterial activity of colloidal platinum nanoparticles (CPNs) toward Streptococcus mutans (S. mutans) viability. S. mutans 109c was treated with water and three CPN solutions at 37°C for 24 h (i.e., control, PAA-Pt, C-Pt, C-CyD-Pt). Dilution series (10-1-10-5) were prepared using brain heart infusion (BHI) broth for all samples, and a 100 µL suspension of each dilution was spread onto a BHI agar plate. Colony-forming units (CFU/mL) were determined after 24 h. The effects of CPNs on S. mutans survival and biofilm formation were investigated using fluorescence and scanning electron microscopies. The antibacterial rate of S. mutans increased with increasing concentrations of all three CPNs, with PAA-Pt nanoparticles exhibiting the highest antibacterial efficacy. CPNs were found to reduce S. mutans growth and inhibit biofilm formation remarkably.
  • Gargling with povidone iodine has a short-term inhibitory effect on SARS-CoV-2 in patients with COVID-19
    T. Seikai; A. Takada; A. Hasebe; M. Kajihara; K. Okuya; T. Sekiguchi (Yamada); W. Kakuguchi; S. Konno; Y. Ohiro
    Journal of Hospital Infection, 123, 179, 181, Elsevier BV, May 2022, [Peer-reviewed]
    Scientific journal
  • Oral frailty and carriage of oral Candida in community-dwelling older adults (Check-up to discover Health with Energy for senior Residents in Iwamizawa; CHEER Iwamizawa).
    Haruhisa Baba; Yutaka Watanabe; Kazuhito Miura; Kimiya Ozaki; Takae Matsushita; Miyako Kondoh; Kazutaka Okada; Akira Hasebe; Tokiyoshi Ayabe; Kiminori Nakamura; Shinji Nakaoka; Katsuhiko Ogasawara; Teppei Suzuki; Hiroshi Saito; Takashi Kimura; Akiko Tamakoshi; Yutaka Yamazaki
    Gerodontology, 39, 1, 49, 58, Mar. 2022, [Peer-reviewed], [International Magazine]
    English, Scientific journal, OBJECTIVE: To examine the association between oral frailty and oral Candida carriage as a general indicator of deteriorating oral function in older adults. BACKGROUND: Older adults exhibit an elevated risk of oral candidiasis caused by Candida. Although many studies have identified factors associated with oral Candida carriage, none have evaluated its relationship with oral function. MATERIALS AND METHODS: This study included 210 community-dwelling older adults aged ≥60 years who participated in wellness checks. Fungal flora expression in saliva samples was evaluated to identify oral C. albicans and C. glabrata. Participants were categorised by detection of neither strain (group 1), either one of the strains (group 2), or both strains (group 3). The relationship between oral Candida carriage and oral frailty was evaluated by multinomial logistic regression analysis. RESULTS: The participants included 58 men and 152 women with a mean age of 74.2 ± 6.1 years. A total of 88 (41.9%), 94 (44.8%) and 28 (13.3%) participants were assigned to groups 1, 2 and 3 respectively. In the multinomial logistic regression analysis, significant associations were observed between group 1 and group 2 for "Have you choked on your tea or soup recently?" and the number of applicable oral frailty items. Between group 1 and group 3, significant associations were observed for the number of remaining teeth, masticatory performance and the number of applicable oral frailty items. CONCLUSION: We obtained basic data useful for intervention studies aimed at verifying whether oral function management prevents deterioration of the oral bacterial flora.
  • Controlled release, antimicrobial activity, and oral mucosa irritation of cetylpyridinium chloride-montmorillonite incorporated in a tissue conditioner.
    Erika Asahara; Yasuhiko Abe; Kiichi Nakamori; Yohei Okazaki; Yoji Makita; Akira Hasebe; Kazuhiro Tsuga; Atsuro Yokoyama
    Dental materials journal, 41, 1, 142, 149, 23 Sep. 2021, [Peer-reviewed], [Domestic magazines]
    English, Scientific journal, This study examined the controlled release of cetylpyridinium chloride (CPC) from a tissue conditioner (TC) containing CPC-montmorillonite (CPC-Mont), the associated antimicrobial activity, and oral mucosa irritation. The CPC release test was performed daily for 28 days in three test solutions: distilled water, 0.2 M NaCl, and 0.2 M HCl. The antimicrobial activities for 7, 14, 21, and 28 days against Candida albicans, Staphylococcus aureus, and Streptococcus mutans were assessed according to the JIS Z 2801/ISO 22196 standard. An oral mucosa irritation test was conducted using cheek pouches in five male hamsters according to the ISO 10993-10:2010 standard. The amount of CPC released each day and the cumulative amount released over 28 days (6.12 mg) were less than the daily safe maximum of sore throat medicines (8 mg). Additionally, TC with CPC-Mont could sustain antimicrobial activity against adherent bacteria for 14 days and has no oral mucosa irritation potential.
  • TLR2 signals triggerd by mycoplasmal lipoprotein/lipopeptide induce K+ efflux to activate the NLRP3 inflammasome
    Ayumi Saeki; Takeshi Into; Hideo Kataoka; Akira Hasebe; Ken-ichiro Shibata
    Hokkaido J. Dent. Sci., 42, 52, 57, Sep. 2021, [Peer-reviewed]
    English, Scientific journal
  • Naringenin suppresses Toll-like receptor 2-mediated inflammatory responses through inhibition of receptor clustering on lipid rafts.
    Hideo Kataoka; Ayumi Saeki; Akira Hasebe; Ken-Ichiro Shibata; Takeshi Into
    Food science & nutrition, 9, 2, 963, 972, Feb. 2021, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Toll-like receptors (TLRs) are important innate immune receptors that sometimes cause excessive inflammatory responses and a perpetuated inflammatory loop that can be involved in inflammatory and autoimmune diseases. TLR2 recognizes bacterial lipoproteins in association with TLR1 or TLR6, and triggers inflammatory responses through activation of the transcription factor NF-κB. Naringenin, a type of citrus flavonoid, has been shown to possess anti-inflammatory properties, but its detailed action against TLR2 remains to be fully elucidated. The present study was designed to determine whether naringenin affects the inflammatory responses triggered by TLR2. Naringenin inhibited proinflammatory cytokine production and attenuated NF-κB activation in cells stimulated with a synthetic triacylated-type lipopeptide known as a TLR2/TLR1 ligand, as well as a synthetic diacylated-type lipopeptide known as a TLR2/TLR6 ligand. Moreover, a similar inhibitory effect was observed in cells stimulated with a crude lipophilic fraction extracted from Staphylococcus aureus cell walls and in cells stimulated with S. aureus cells. Furthermore, we showed that such an effect is caused by inhibition of TLR2 clustering in lipid rafts on the cell membrane. These results suggest that naringenin suppresses the inflammatory responses induced by TLR2 signal transduction. Our findings indicate a novel anti-inflammatory property of naringenin, mediated through the regulation of cell surface TLR2 functioning.
  • Factor associated with oral candidiasis caused by co-infection of Candida albicans and Candida glabrata: A retrospective study
    Hiroyuki Hato; Ken ichiro Sakata; Jun Sato; Akira Hasebe; Yutaka Yamazaki; Yoshimasa Kitagawa
    Journal of Dental Sciences, 2021, [Peer-reviewed]
    Scientific journal
  • Lipoprotein Extraction from Microbial Membrane and Lipoprotein/Lipopeptide Transfection into Mammalian Cells.
    Akira Hasebe; Ayumi Saeki; Ken-Ichiro Shibata
    Methods in molecular biology (Clifton, N.J.), 2210, 195, 204, 2021, [Invited], [Lead author, Corresponding author], [International Magazine]
    English, Scientific journal, Microbial lipoproteins/lipopeptides are important virulence factors for periodontal diseases. The membrane lipoproteins from Mycoplasma salivarium or Tannerella forsythia can be easily extracted by exploiting a characteristic feature of Triton X-114: its aqueous nature at low temperatures (0-4 °C), which is absent at room temperature (25-37 °C). Transfection of these lipopeptides into macrophages was performed using the protein transfection reagent, PULSin.
  • Development of tissue conditioner containing cetylpyridinium chloride montmorillonite as new antimicrobial agent: Pilot study on antimicrobial activity and biocompatibility.
    Tsubasa Naoe; Akira Hasebe; Rumi Horiuchi; Yoji Makita; Yohei Okazaki; Keisuke Yasuda; Kenya Matsuo; Yasuhiro Yoshida; Kazuhiro Tsuga; Yasuhiko Abe; Atsuro Yokoyama
    Journal of prosthodontic research, 64, 4, 436, 443, Oct. 2020, [Peer-reviewed], [Domestic magazines]
    English, Scientific journal, PURPOSE: The mechanical properties, antimicrobial activity, and biocompatibility of a novel antimicrobial tissue conditioner containing cetylpyridinium chloride with montmorillonite (CPC-Mont) were evaluated. METHODS: To examine the mechanical properties of the novel material, hardness, consistency, and penetration tests were conducted. Antimicrobial activity against Candida albicans (C. albicans) and Staphylococcus aureus (S. aureus) was evaluated. Cell viabilities of fibroblasts and epithelial cells using eluates from materials were measured to evaluate cytotoxicity. In addition, to assess tissue response, animal experiments were conducted. RESULTS: The hardness test results were similar to those of other commercially available materials. The novel tissue conditioner showed good antimicrobial activity against C. albicans and S. aureus compared with other materials. This effect was sustained for a week for C. albicans. In the case of S. aureus, microbial growth was suppressed for up to 3 weeks. Cell viability of the novel material for the eluate at 1 day was significantly less than those of other material for both cells. However, the cell viability at 7 days showed no significant difference. Animal experiments demonstrated that inflammatory responses around materials were not observed on the oral mucosa as other material. CONCLUSION: Within the limitations of this in vitro and in vivo study, the results suggest that the newly developed tissue conditioner containing CPC-Mont has not only excellent antimicrobial properties, but also the same mechanical properties and biocompatibility as tissue conditioners on the market.
  • Gasdermin D-independent release of interleukin-1β by living macrophages in response to mycoplasmal lipoproteins and lipopeptides.
    Ayumi Saeki; Kohsuke Tsuchiya; Takashi Suda; Takeshi Into; Akira Hasebe; Toshihiko Suzuki; Ken-Ichiro Shibata
    Immunology, 161, 2, 114, 122, Oct. 2020, [Peer-reviewed], [International Magazine]
    English, Scientific journal, Interleukin-1β (IL-1β) plays pivotal roles in controlling bacterial infections and is produced after the processing of pro-IL-1β by caspase-1, which is activated by the inflammasome. In addition, caspase-1 cleaves the cytosolic protein, gasdermin-D (GSDMD), whose N-terminal fragment subsequently forms a pore in the plasma membrane, leading to the pyroptic cell-death-mediated release of IL-1β. Living cells can also release IL-1β via GSDMD pores or other unconventional secretory pathways. However, the precise mechanisms are poorly defined. Here, we show that lipoproteins from Mycoplasma salivarium (MsLP) and Mycoplasma pneumoniae (MpLP) and an M. salivarium-derived lipopeptide (FSL-1), which are activators of the nucleotide-binding oligomerization domain-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome, induce IL-1β release from mouse bone-marrow-derived macrophages (BMMs) without inducing cell death. The levels of IL-1β release induced by MsLP, MpLP and FSL-1 were more than 100 times lower than those induced by the canonical NLRP3 activator nigericin. The IL-1β release-inducing activities of MsLP, MpLP and FSL-1 were not attenuated in BMMs from GSDMD-deficient mice. Furthermore, both active caspase-1 and cleaved GSDMD were detected in response to transfection of FSL-1 into the cytosol of BMMs, but the release of IL-1β was unaffected by GSDMD deficiency. Meanwhile, punicalagin, a membrane-stabilizing agent, drastically down-regulated the release of IL-1β in response to FSL-1. These results suggest that mycoplasmal lipoprotein/lipopeptide-induced IL-1β release by living macrophages is not mediated via GSDMD but rather through changes in membrane permeability.
  • Differences in interleukin-1β release-inducing activity of Candida albicans toward dendritic cells and macrophages.
    Akira Hasebe; Ayumi Saeki; Yasuhiro Yoshida; Ken-Ichiro Shibata
    Archives of Oral Biology, 93, 115, 125, Jun. 2018, [Peer-reviewed], [Lead author], [International Magazine]
    English, Scientific journal, OBJECTIVE: The purpose of this study is to elucidate differences in the mechanism of the IL-1β release-inducing activity of Candida albicans toward dendritic cells and macrophages because IL-1β is one of the proinflammatory cytokines which is crucial in host defense against candidiasis. DESIGN: Two C. albicans strains were used in this study. One strain is uridine-auxotrophic (CAI4) that needs uridine to grow and form hyphae, and another is a strain without any specific auxotrophy (pACT1-GFP), which forms hyphae naturally by culturing with serum components. Murine macrophage and dendritic cell lines were primed with LPS and then stimulated with C. albicans CAI4 or pACT1-GFP. RESULTS: Both strains of C. albicans induced IL-1β release from dendritic cells, and C. albicans pACT1-GFP induced IL-1β release but CAI4 induced little amounts in macrophages. These differences were suggested to be due to the difference in the amount of extracellular ATP released in the cell culture supernatants induced by C. albicans CAI4 or pACT1-GFP. For induction of IL-1β release from both macrophages and dendritic cells by C. albicans, direct contacts of the microbes with cells were required. In addition, macrophages required morphological change of C. albicans from yeast to hyphae for induction of IL-1β release, whereas dendritic cells did not require it. Dead C. albicans could induce IL-1β release from dendritic cells, but could not from macrophages. CONCLUSIONS: There are different mechanisms by which C. albicans induces IL-1β release from dendritic cells and macrophages.
  • Activation of NLRP3 inflammasome in macrophages by mycoplasmal lipoproteins and lipopeptides
    Saeki, A.; Sugiyama, M.; Hasebe, A.; Suzuki, T.; Shibata, K.
    Molecular Oral Microbiology, 33, 4, Apr. 2018, [Peer-reviewed]
    English, Scientific journal
  • Aggregatibacter actinomycetemcomitansのゲノムDNAはマクロファージに対してnucleotide-binding domain-like receptor containing protein 3インフラマソームを活性化してIL-1βを誘導する
    亀崎 良助; 阿部 亜美; 佐伯 歩; 長谷部 晃; 鈴木 敏彦; 北川 善政; 柴田 健一郎
    北海道歯学雑誌, 38, 2, 177, 184, 北海道歯学会, Mar. 2018, [Peer-reviewed]
    Japanese, インフラマソームは多様な生理活性をもつ炎症性サイトカインの一つであるIL-1βの産生を制御する細胞内センサーである。IL-1βは歯周炎を含む多くの炎症性疾患において重要な病因的役割を果たしている。そこで、本研究では、侵襲性歯周炎の主な病原菌であるAggregatibacter actinomycetemcomitansによるnucleotide-binding domain-like receptor containing protein 3(NLRP3)インフラマソームの活性化を介したIL-1β産生誘導について検証した。C57BL/6(B6)マウスならびにcaspase-1、ASC(apoptosis-associated speck-like protein containing a caspase recruitment domain)あるいはNLRP3をノックアウトしたマウスより採取した骨髄細胞から分化誘導したマクロファージ(BMM)をA.actinomycetemcomitans JP2の生菌および100℃で5分間熱処理した死菌で刺激した。IL-1βはELISA法ならびにウェスタンブロッティング法で測定した。生菌ならびに死菌でB6 BMMを刺激したところ、生菌、死菌ともにIL-1βの産生を誘導したが、生菌に比べて死菌の活性が約10倍高かった。生菌およ
  • Charge and controlled release of epigallocatechin gallate by glass ionomer cement containing nanoporous silica particles
    Koichi Nakamura; Ko Nakanishi; Yosuke Bando; Akira Hasebe; Atsushi Hyono; Shigeaki Abe; Ken-Ichiro Shibata; Yasuhiro Yoshida; Junichiro Iida; Yasutaka Yawaka
    Nano Biomedicine, 9, 1, 29, 34, National Institute of Informatics, 2018, [Peer-reviewed]
    English, Scientific journal
  • Activation of nucleotide-binding domain-like receptor containing protein 3 inflammasome in dendritic cells and macrophages by Streptococcus sanguinis
    Ayumi Saeki; Toshihiko Suzuki; Akira Hasebe; Ryousuke Kamezaki; Mari Fujita; Futoshi Nakazawa; Ken-Ichiro Shibata
    CELLULAR MICROBIOLOGY, 19, 3, Mar. 2017, [Peer-reviewed]
    English, Scientific journal
  • Aggregatibacter actinomycetemcomitans DNAによるインフラマソームの活性化
    亀崎 良助; 佐伯 歩; 長谷部 晃; 北川 善政; 鈴木 敏彦; 柴田 健一郎
    Journal of Oral Biosciences Supplement, 2016, 374, 374, (一社)歯科基礎医学会, Sep. 2016
    Japanese
  • Activation of inflammasomes in dendritic cells and macrophages by Mycoplasma salivarium
    M. Sugiyama; A. Saeki; A. Hasebe; R. Kamesaki; Y. Yoshida; Y. Kitagawa; T. Suzuki; K. Shibata
    MOLECULAR ORAL MICROBIOLOGY, 31, 3, 259, 269, Jun. 2016, [Peer-reviewed]
    English, Scientific journal
  • Age-related alteration of expression and function of TLRs and NK activity in oral candidiasis
    M. Oouchi; A. Hasebe; H. Hata; T. Segawa; Y. Yamazaki; Y. Yoshida; Y. Kitagawa; K-I Shibata
    ORAL DISEASES, 21, 5, 645, 651, Jul. 2015, [Peer-reviewed], [Lead author]
    English, Scientific journal
  • Activation of inflammasome by Aggregatibacter actinomycetemcomitans
    阿部亜美; 佐伯歩; 長谷部晃; 原博志; 八若保孝; 柴田健一郎
    北海道歯学雑誌, 35, 2, 123, 132, 北海道歯学会, 15 Mar. 2015, [Peer-reviewed]
    Japanese
  • In vivo anti-tumor activity of oral Streptococci
    原博志; 長谷部晃; 佐伯歩; 阿部亜美; 山崎裕; 柴田健一郎
    北海道歯学雑誌, 35, 1, 16, 24, 北海道歯学会, 15 Sep. 2014, [Peer-reviewed]
    Japanese
  • Roles of the Src family kinase Lck in Toll-like receptor 2 signaling
    谷詰直穂; 大谷誠; 長谷部晃; 佐伯歩; 戸塚靖則; 鄭漢忠; 柴田健一郎
    北海道歯学雑誌, 35, 1, 8, 15, 北海道歯学会, 15 Sep. 2014, [Peer-reviewed]
    Japanese
  • A Potential Pathogenic Factor from Mycoplasma hominis is a TLR2-Dependent, Macrophage-Activating, P50-Related Adhesin
    Akira Hasebe; Hong-Hua Mu; Barry C. Cole
    AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, 72, 3, 285, 295, Sep. 2014, [Peer-reviewed], [Lead author], ［Internationally co-authored］
    English, Scientific journal
  • Toll-like receptor 2-mediated modulation of growth and functions of regulatory T cells by oral streptococci
    A. Saeki; T. Segawa; T. Abe; M. Sugiyama; T. Arimoto; H. Hara; A. Hasebe; M. Ohtani; N. Tanizume; M. Ohuchi; H. Kataoka; M. Kawanami; A. Yokoyama; K. Shibata
    MOLECULAR ORAL MICROBIOLOGY, 28, 4, 267, 280, Aug. 2013, [Peer-reviewed]
    English, Scientific journal
  • Mycoplasma removal from cell culture using antimicrobial photodynamic therapy
    Akira Hasebe; Isao Ishikawa; Haque M. Shamsul; Makoto Ohtani; Taku Segawa; Ayumi Saeki; Naoho Tanizume; Manabu Oouchi; Yoshihide Okagami; Teruo Okano; Ken-Ichiro Shibata
    Photomedicine and Laser Surgery, 31, 3, 125, 131, 3, 01 Mar. 2013, [Peer-reviewed], [Lead author]
    English, Scientific journal
  • Differences in recognition of wild-type and lipoprotein-deficient strains of oral Streptococci in vitro and in vivo
    Taku Segawa; Ayumi Saeki; Akira Hasebe; Takafumi Arimoto; Hideo Kataoka; Atsuro Yokoyama; Masamitsu Kawanami; Ken-ichiro Shibata
    Pathogens and Disease, 68, 3, 65, 77, 3, 2013, [Peer-reviewed]
    English, Scientific journal
  • Involvement of suppressor of cytokine signalling-1-mediated degradation of MyD88-adaptor-like protein in the suppression of Toll-like receptor 2-mediated signalling by the murine C-type lectin SIGNR1-mediated signalling
    Makoto Ohtani; Mitsuhiro Iyori; Ayumi Saeki; Naoho Tanizume; Takeshi Into; Akira Hasebe; Yasunori Totsuka; Ken-ichiro Shibata
    CELLULAR MICROBIOLOGY, 14, 1, 40, 57, Jan. 2012, [Peer-reviewed]
    English, Scientific journal
  • In vivo anti- and pro-tumour activities of the TLR2 ligand FSL-1
    Kazuto Kiura; Akira Hasebe; Ayumi Saeki; Taku Segawa; Futoshi Okada; Haque Mohammad Shamsul; Makoto Ohtani; Takeshi Into; Nobuo Inoue; Minoru Wakita; Ken-ichiro Shibata
    IMMUNOBIOLOGY, 216, 8, 891, 900, Aug. 2011, [Peer-reviewed], [Lead author]
    English, Scientific journal
  • Novel interactions of a microbial superantigen with TLR2 and TLR4 differentially regulate IL-17 and Th17-associated cytokines
    Hong-Hua Mu; Akira Hasebe; Adam Van Schelt; Barry C. Cole
    CELLULAR MICROBIOLOGY, 13, 3, 374, 387, Mar. 2011, [Peer-reviewed]
    English, Scientific journal
  • The Toll-like receptor 2 (TLR2) ligand FSL-1 is internalized via the clathrin-dependent endocytic pathway triggered by CD14 and CD36 but not by TLR2
    Haque M. Shamsul; Akira Hasebe; Mitsuhiro Iyori; Makoto Ohtani; Kazuto Kiura; Diya Zhang; Yasunori Totsuka; Ken-ichiro Shibata
    IMMUNOLOGY, 130, 2, 262, 272, Jun. 2010, [Peer-reviewed], [Lead author]
    English, Scientific journal
  • Relationship of expression and function of Toll-like receptor 2 and 4 with aging in human and mouse.
    Donen M; Ohtani M; Kiura K; Saeki A; Tanizume N; Hasebe A; Totsuka Y; Shibata K
    Hokkaido Journal of Dental Science, 31, 82, 89, 2010, [Peer-reviewed]
  • A role of the Ca(2+) binding site of DC-SIGN in the phagocytosis of E. coli
    Mitsuhiro Iyori; Makoto Ohtani; Akira Hasebe; Yasunori Totsuka; Ken-ichiro Shibata
    BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 377, 2, 367, 372, Dec. 2008, [Peer-reviewed]
    English, Scientific journal
  • Resveratrol modulates phagocytosis of bacteria through an NF-kappa B-dependent gene program
    Mitsuhiro Iyori; Hideo Kataoka; Haque Mohammad Shamsul; Kazuto Kiura; Motoaki Yasuda; Takashi Nakata; Akira Hasebe; Ken-ichiro Shibata
    ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 52, 1, 121, 127, Jan. 2008, [Peer-reviewed]
    English, Scientific journal
  • マクロファージにおけるジアシルリポペプチドFSL-1刺激による遺伝子発現の網羅的解析とFSL-1の取り込み様式
    長谷部晃; Haque Mohammad Shamsul; 伊従光洋; 木浦和人; 大谷誠; 柴田健一郎
    日本マイコプラズマ学会雑誌, 35, 79, 83, 2008
    Japanese, Scientific journal
  • Inflammatory lipoproteins purified from a toxigenic and arthritogenic strain of Mycoplasma arthritidis are dependent on Toll-like receptor 2 and CD14
    Akira Hasebe; Hong-Hua Mu; Leigh R. Washburn; Fok V. Chan; Nathan D. Pennock; Michael L. Taylor; Barry C. Cole
    INFECTION AND IMMUNITY, 75, 4, 1820, 1826, Apr. 2007, [Peer-reviewed], [Lead author]
    English, Scientific journal
  • The diacylated lipopeptide FSL-1 enhances phagocytosis of bacteria by macrophages through a Toll-like receptor 2-mediated signalling pathway
    Masako Mae; Mitsuhiro Iyori; Motoaki Yasuda; Haque Mohammad Shamsul; Hideo Kataoka; Kazuto Kiura; Akira Hasebe; Yasunori Totsuka; Ken-ichiro Shibata
    FEMS IMMUNOLOGY AND MEDICAL MICROBIOLOGY, 49, 3, 398, 409, Apr. 2007, [Peer-reviewed]
    English, Scientific journal
  • A microbial TLR2 agonist imparts macrophage-activating ability to apolipoprotein A-1
    Akira Hasebe; Nathan D. Pennock; Hong-Hua Mu; Fok V. Chan; Michael L. Taylor; Barry C. Cole
    JOURNAL OF IMMUNOLOGY, 177, 7, 4826, 4832, Oct. 2006, [Peer-reviewed], [Lead author]
    English, Scientific journal
  • Isolation and partial purification of macrophage- and dendritic cell-activating components from Mycoplasma arthritidis: Association with organism virulence and involvement with toll-like receptor 2
    BC Cole; HH Mu; ND Pennock; A Hasebe; FV Chan; LR Washburn; MR Peltier
    INFECTION AND IMMUNITY, 73, 9, 6039, 6047, Sep. 2005, [Peer-reviewed]
    English, Scientific journal
  • Biological activities of Bacteroides forsythus lipoproteins and their possible pathological roles in periodontal disease
    A Hasebe; A Yoshimura; T Into; H Kataoka; S Tanaka; S Arakawa; H Ishikura; DT Golenbock; T Sugaya; N Tsuchida; M Kawanami; Y Hara; K Shibata
    INFECTION AND IMMUNITY, 72, 3, 1318, 1325, Mar. 2004, [Peer-reviewed], [Lead author]
    English, Scientific journal
  • Relationship between structures and biological activities of mycoplasmal diacylated lipopeptides and their recognition by toll-like receptors 2 and 6
    T Okusawa; M Fujita; JI Nakamura; T Into; M Yasuda; A Yoshimura; Y Hara; A Hasebe; DT Golenbock; M Morita; Y Kuroki; T Ogawa; KI Shibata
    INFECTION AND IMMUNITY, 72, 3, 1657, 1665, Mar. 2004, [Peer-reviewed]
    English, Scientific journal
  • Stimulation of human Toll-like receptor (TLR) 2 and TLR6 with membrane lipoproteins of Mycoplasma fermentans induces apoptotic cell death after NF-kappa B activation
    T Into; K Kiura; M Yasuda; H Kataoka; N Inoue; A Hasebe; K Takeda; S Akira; K Shibata
    CELLULAR MICROBIOLOGY, 6, 2, 187, 199, Feb. 2004, [Peer-reviewed]
    English, Scientific journal
  • Synergic effects of mycoplasmal lipopeptides and extracellular ATP on activation of macrophages
    T Into; M Fujita; T Okusawa; A Hasebe; M Morita; KI Shibata
    INFECTION AND IMMUNITY, 70, 7, 3586, 3591, Jul. 2002, [Peer-reviewed]
    English, Scientific journal
  • Mycoplasmal lipoproteins induce toll-like receptor 2-and caspases-mediated cell death in lymphocytes and monocytes
    T Into; Y Nodasaka; A Hasebe; T Okuzawa; J Nakamura; N Ohata; K Shibata
    MICROBIOLOGY AND IMMUNOLOGY, 46, 4, 265, 276, 2002, [Peer-reviewed]
    English, Scientific journal
  • Signaling pathways induced by lipoproteins derived from Mycoplasma salivarium and a synthetic lipopeptide (FSL-1) in normal human gingival fibroblasts
    J Nakamura; K Shibata; A Hasebe; T Into; T Watanabe; N Ohata
    MICROBIOLOGY AND IMMUNOLOGY, 46, 3, 151, 158, 2002, [Peer-reviewed]
    English, Scientific journal
  • A 4.1-kilodalton polypeptide in the cultural supernatant of Mycoplasma fermentans is one of the substances responsible for induction of interleukin-6 production by human gingival fibroblasts
    A Hasebe; K Shibata; T Watanabe
    INFECTION AND IMMUNITY, 69, 11, 7173, 7177, Nov. 2001, [Peer-reviewed], [Lead author]
    English, Scientific journal
  • 微生物の有するモジュリン
    長谷部 晃; 柴田 健一郎
    北海道歯学雑誌, 22, 109, 122, 2001, [Peer-reviewed]
    Japanese, Scientific journal
  • The N-terminal lipopeptide of a 44-kDa membrane-bound lipoprotein of Mycoplasma salivarium is responsible for the expression of intercellular adhesion molecule-1 on the cell surface of normal human gingival fibroblasts
    K Shibata; A Hasebe; T Into; M Yamada; T Watanabe
    JOURNAL OF IMMUNOLOGY, 165, 11, 6538, 6544, Dec. 2000, [Peer-reviewed]
    English, Scientific journal
  • Transcriptional activation of mRNA of intercellular adhesion molecule 1 and induction of its cell surface expression in normal human gingival fibroblasts by Mycoplasma salivarium and Mycoplasma fermentans
    L Dong; KI Shibata; Y Sawa; A Hasebe; Y Yamaoka; S Yoshida; T Watanabe
    INFECTION AND IMMUNITY, 67, 6, 3061, 3065, Jun. 1999, [Peer-reviewed]
    English, Scientific journal
  • Detection of Mycoplasma fermentans in saliva sampled from infants, preschool and school children, adolescents and adults by a polymerase chain reaction-based assay
    K Shibata; M Kaga; M Kudo; L Dong; A Hasebe; H Domon; Y Sato; H Oguchi; T Watanabe
    MICROBIOLOGY AND IMMUNOLOGY, 43, 6, 521, 525, 1999, [Peer-reviewed]
    English, Scientific journal
  • Partial purification and characterization of the active entity responsible for inducing interleukin-6 production by human gingival fibroblasts from Mycoplasma salivarium cells
    A Hasebe; K Shibata; H Domon; L Dong; T Watanabe
    MICROBIOLOGY AND IMMUNOLOGY, 43, 11, 1003, 1008, 1999, [Peer-reviewed], [Lead author]
    English, Scientific journal
  • Detection of Mycoplasma salivarium and Mycoplasma fermentans in synovial fluids of temporomandibular joints of patients with disorders in the joints
    T Watanabe; K Shibata; T Yoshikawa; L Dong; A Hasebe; H Domon; T Kobayashi; Y Totsuka
    FEMS IMMUNOLOGY AND MEDICAL MICROBIOLOGY, 22, 3, 241, 246, Nov. 1998, [Peer-reviewed]
    English, Scientific journal
  • Mycoplasma salivarium induces interleukin-6 and interleukin-8 in human gingival fibroblasts
    K Shibata; A Hasebe; T Sasaki; T Watanabe
    FEMS IMMUNOLOGY AND MEDICAL MICROBIOLOGY, 19, 4, 275, 283, Dec. 1997, [Peer-reviewed]
    English, Scientific journal
■ Other Activities and Achievements
■ Books and other publications
■ Lectures, oral presentations, etc.
  • 最近注目の常在菌叢と全身の健康の関係について
    長谷部 晃
    北海道子供の歯を守る会・第103回会員研修会, 07 Dec. 2024, Public discourse
    [Invited]
  • Intersection Pathways: Chronic Periodontitis, Cognitive Decline, and Emerging Therapeutic Frontiers
    Lee JW; Hasebe A.
    第97回日本細菌学会総会 総会長シンポジウム「北海道から細菌学を発信する」, 09 Aug. 2024, English, Nominated symposium
    [Invited]
  • 口腔に留まらない口腔細菌の全身状態への関わり
    長谷部 晃
    OralStudio Meeting 2023【歯科疾患の今・修復材料の源流・口腔の先を知る】, 14 Oct. 2023, Public discourse
    [Invited]
  • 腸内細菌だけじゃない！意外と全身状態に関与する口腔細菌
    長谷部 晃
    Oral Studio Web セミナー, 21 Dec. 2021, Public discourse
    [Invited]
  • 自然免疫によるマイコプラズマ由来リポペプチドの認識と処理－マクロファージによるジアシルリポペプチドFSL-1の取り込み機構について
    長谷部 晃
    日本マイコプラズマ学会第39回学術集会, 24 May 2012, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • Mycoplasma arthritidis による関節炎―MAM & リポタンパク質．
    長谷部 晃
    日本マイコプラズマ学会第36回学術集会, 04 Jun. 2009, Japanese, Invited oral presentation
    [Invited], [Domestic Conference]
  • The uptake manner of the diacylated lipopeptide FSL-1 by macrophages
    HASEBE Akira
    Innate Immunity Symposium, Regulation in Innate Immunity - from Recognition Molecules to Antimicrobial Peptides., 29 Oct. 2008, English, Invited oral presentation
    [Invited], [International presentation]
■ Syllabus
  • 発表・論文執筆法演習Ⅰ, 2024年, 博士後期課程, 歯学院
  • 発表・論文執筆法演習Ⅱ, 2024年, 博士後期課程, 歯学院
  • 発表・論文執筆法演習Ⅲ, 2024年, 博士後期課程, 歯学院
  • 教育実習技法, 2024年, 博士後期課程, 歯学院
  • 歯学研究セミナー, 2024年, 博士後期課程, 歯学院
  • 口腔感染制御学, 2024年, 博士後期課程, 歯学院
  • 口腔感染制御学研究, 2024年, 博士後期課程, 歯学院
  • 口腔生物学と医学, 2024年, 博士後期課程, 歯学院
  • 口腔分子免疫学, 2024年, 博士後期課程, 歯学院
  • 口腔分子免疫学研究, 2024年, 博士後期課程, 歯学院
  • 歯学研究概論, 2024年, 博士後期課程, 歯学院
  • 基本技法, 2024年, 博士後期課程, 歯学院
  • 有害・危険物質の取り扱いと管理, 2024年, 博士後期課程, 歯学院
  • 健康と社会, 2024年, 学士課程, 全学教育
  • 関連臨床医学, 2024年, 学士課程, 歯学部
  • フロンティア発展科目, 2024年, 学士課程, 歯学部
  • 健康と社会, 2024年, 学士課程, 全学教育
  • フロンティア基礎科目, 2024年, 学士課程, 歯学部
  • 微生物学・口腔微生物学実習, 2024年, 学士課程, 歯学部
  • 微生物学・口腔微生物学Ⅰ, 2024年, 学士課程, 歯学部
  • 微生物学・口腔微生物学Ⅱ, 2024年, 学士課程, 歯学部
  • 全人教育演習, 2024年, 学士課程, 歯学部
  • アクティブラーニング科目Ⅳ, 2024年, 学士課程, 歯学部
  • 健康と社会, 2024年, 学士課程, 全学教育
■ Affiliated academic society
  • 2023
    The International Organization for Mycoplasmology
  • 日本免疫学会
  • 日本細菌学会
  • 日本マイコプラズマ学会
  • 歯科基礎医学会
■ Research Themes
  • メタゲノム解析・光工学・AIを融合した革新的細菌可視化法の創出とう蝕治療への応用
    科学研究費助成事業
    01 Apr. 2026 - 31 Mar. 2030
    福山 麻衣; ISLAM RAFIQUL; 友清 淳; 戸井田 侑; 星加 修平; 川本 千春; 槌谷 賢太; 兼子 裕史; 長谷部 晃
    日本学術振興会, 基盤研究(C), 北海道大学, 26K12674
  • successful aging-口腔内細菌攻略より
    科学研究費助成事業
    01 Apr. 2025 - 31 Mar. 2028
    箕輪 和行; 亀田 浩之; 長谷部 晃
    日本学術振興会, 基盤研究(C), 北海道大学, 25K13282
  • 脂質ラフトを標的とする新しい麻酔メカニズム研究－バイオイメージングの活用－
    科学研究費助成事業
    01 Apr. 2025 - 31 Mar. 2028
    長谷 由理; 樺山 一哉; 長谷部 晃; 舩橋 誠
    日本学術振興会, 基盤研究(C), 北海道大学, 25K12181
  • Analysis of common bacteria in the oral cavity involved in the acquisition of malignant transformation of oral cancer.
    Grants-in-Aid for Scientific Research
    01 Apr. 2023 - 31 Mar. 2026
    大廣 洋一; 樋田 京子; 長谷部 晃
    2023年度は適切な症例の抽出を行い，臨床ならびに病理組織学的な背景を明確にすることに専念した．対象とした症例は，2015年から2018年に当科で加療した症例で，初診時に転移のない10例とした．性別は，男性7例，女性3例で，年齢は35～85歳で中央値は51歳であった．うち5例は後発転移を来した症例を含めた．後発転移までの期間は１か月～2年6か月で中央値は12か月であった．腫瘍原発の大きさは4～27mmで中央値は20mmであった．臨床的な腫瘍の浸潤の深さは，1から9.5mmで中央値は6mmであった．臨床的T分類は，第7版UICC分類でT1は7例，T2は3例で，第8版UICC分類でT1は4例，T2は6例であった．ついで，病理組織学的背景を検索した．腫瘍の病理組織学的な浸潤の深さは4.6±3.13mmであった．一般的に腫瘍の悪性度評価方法として用いられる腫瘍宿主境界部の腫瘍胞巣の形態に注目した腫瘍の浸潤様式をあらわす各指標の詳細は，リンパ節転移と比較的挿管すると言われる山本-古浜（YK）分類は全例YK-3で，最も予後不良と言われているYK-4Dは認めなかった．腫瘍の浸潤深さが4mm以上で局所再発や疾患特異的生存率の有意な予後予測因子とわれるWorst Pattern of Invasion-5は全例Grade3であった．消化器癌の予後予測で用いられる蔟（ぞく）出（Tumor budding）は，BD-1；8例，BD-2; 2であった．組織学的悪性はGrade I；8例，Grade II；2例であった．また，筋層浸潤は後発転移ありで4例，後発転移なしで3例に認めた. 脈管侵襲は，リンパ管侵襲ならびに静脈侵襲をいずれも認めなかった．神経周囲浸潤も全例で認めなかった．
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, 23K09367
  • 歯周病細菌の脳への移行トレース
    科学研究費助成事業
    Apr. 2022 - Mar. 2025
    箕輪 和行; 亀田 浩之; 長谷部 晃
    日本学術振興会, 基盤研究(C), 北海道大学, 22K10333
  • Development of Oral Cancer Prevention Methods Based on Analysis of Oral Bacterial Flora and Inflammatory Cytokines in Saliva
    Grants-in-Aid for Scientific Research
    Apr. 2022 - Mar. 2025
    大賀 則孝; 北川 善政; 坂田 健一郎; 山村 凌大; 佐藤 淳; 園下 将大; 長谷部 晃
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, 22K10163
  • 脂質ラフトのバイオイメージングと電気生理学的手法による全身麻酔薬の作用機序研究
    科学研究費助成事業
    Apr. 2022 - Mar. 2025
    長谷 由理; 舩橋 誠; 長谷部 晃
    日本学術振興会, 基盤研究(C), 北海道大学, 22K09062
  • 全身主要血管壁内における歯周病原性菌の存在分布ー脳血管障害による死亡例をもとに
    科学研究費助成事業
    Apr. 2020 - Mar. 2023
    竹内 明子; 的場 光太郎; 箕輪 和行; 兵頭 秀樹; 亀田 浩之; 長谷部 晃
    研究期間２年目では、ご遺体（法医解剖体）における死後CT画像取得時に、全身大血管（大脳動脈、頚動脈、胸部大動脈、腹部大動脈）における壁肥厚やプラークによる血管狭窄に対する画像的検索を進めており、これらの症例数は累計で18件となりました。
    検体採取を行ったそれぞれの症例において画像的検索と法医解剖所見を比較することで、歯周病細菌の存在分布検証に用いる検体（主要血管壁）の採取部位をそれぞれ決定しました。また、採取した血管壁を用いて、凍結切片の作成により、病理学的検索の可能性を模索し、免疫染色による歯周病菌の同定（存在分布の確認）についても追加の検討を行っています。
    予備実験において、死後CT画像にて血管壁に石灰化が見られる場合、DNA採取が困難である場合があり、血管壁の石灰化の度合いに対して、死後CT画像上でのスコア化を追加検討しています。
    また、法医解剖体の口腔内所見採取時に、歯周病進行状況、残存歯数、歯科治療痕等のデータ収集をさらに進めています。検体数の増加により、前年度に取得した歯周ポケット検査による歯周病進行度のスコアに変更が生じたため、再度検討を行っています。検体採取については２年目も順調に進んでいますが、検体数の増加にともない、検体の口腔内所見（残存歯数や歯科治療所見）が多様に見られ、また、高齢のご遺体（解剖体）では、残存歯数が少ない場合があり、初年度に採取した口腔内所見によるスコア化に関して、調整が必要となっています。
    日本学術振興会, 基盤研究(C), 北海道大学, 20K10287
  • How oral candidiasis can exacerbate colitis?
    Grants-in-Aid for Scientific Research
    Apr. 2020 - Mar. 2023
    長谷部 晃; 佐伯 歩
    腸内細菌叢の乱れ（dysbiosis）により、全身の健康状態の悪化を招くことがあるなど、常在菌が全身の状態に影響を及ぼしていることがわかってきている。我々は、嚥下により常時口腔細菌を摂取することで口腔細菌叢が腸内細菌叢におけるdysbiosisにつながり、口腔細菌叢のdysbiosisが全身の健康状態に影響を与えるのではないかと考えている。そこで、口腔にCandida albicansを定着させてC. albicansを常時嚥下するモデルマウスで研究をしている。C. albicanはマウスの消化管には存在せず、ヒト口腔など消化管に常在する日和見病原体である。これまで我々は、マウスがC. albicansを常時嚥下すると腸内細菌叢が大きく変動すること、またその腸内細菌叢の変動により、腸炎の増悪を誘導することも明らかにした。さらにC. albicanを常時嚥下しているマウスにおいては、腸炎を誘導するとoccludinとZO-1などの上皮間接着分子の発現レベルが低下することがわかった。これらのことに基づき、Toll様受容体2（TLR2）欠損（TLR2KO）マウスと野生型のマウスとの間で腸内細菌叢に違いがあるかを調べた。TLR2はC. albicansの宿主による認識において非常に重要な役割を果たす受容体のひとつである。同一ケージで2週間飼育した野生型マウスとTLR2KOマウスの糞便中の細菌についてメタゲノム解析により調べた。その結果、TLR2KOマウス糞便には野生型マウスの場合と比べてグラム陽性菌が多かった。また、グラム陰性桿菌のAkkermansia muciniphilaの割合がTLR2KOマウスにおいて野生型マウスより有意に少ないことがわかった。A. muciniphilaは現在糖尿病や肥満の抑制など多くの点でいわゆる善玉菌として注目されているものであり興味深い。
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, 20K09917
  • Association between oral bacteria and oral cancer metastasis
    Grants-in-Aid for Scientific Research
    Apr. 2019 - Mar. 2023
    大廣 洋一; 北村 哲也; 樋田 京子; 長谷部 晃
    前年度に引き続き、舌がんの後発転移に口腔常在菌が関与するか検討するために、頸部郭清術によって得られた症例より得られた標本において病理組織学的に転移を認めたリンパ節と転移を認めなかったリンパ節の未染色標本からDNAを抽出し、PCRにより細菌由来の16s rDNAを検出した．PCRは再現性が確認されたサイクル数50サイクルにて実施した。手術で切除した頸部郭清組織から摘出したリンパ節において、病理組織学的に転移を認めた症例では腫瘍実質において壊死部分が多く含まれているものが半数以上を占めていた。壊死部分が多いリンパ節では、16s rDNAの発現を認めないか発現が弱いなど、PCRの測定が安定せず、DNA抽出時の試料採取に工夫が必要と考えられた。現在、顕微鏡で確認しながら、壊死部分を含まないように試料を採取する方法について検討している。また、舌がん原発の腫瘍細胞に口腔常在菌が存在するか検討することを行っている。この検討では、腫瘍表層では口腔内に暴露されているため、表在性の部分を避け、腫瘍の深部において細菌由来の16s rDNAが発現しているか検討している。この検討により、病理組織学的に転移ありと判断した７個のリンパ節中に4個でPCRにて16s rDNAの発現を認めたことから転移に16s rDNAの存在が重要か裏打ちの検討になると考えている。また、がん細胞の浸潤能や転移能を亢進し、がんの悪性化に関係するムチン型糖タンパク質ポドプラニンを試験的に6例に対して免疫染色を実施したが、明らかに陽性であったのは2例であった。以上、検討方法および検討した症例数に限りがあるため、本年度も症例の蓄積が必要と考える。
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, 19K10350
  • 口腔カンジダによる腸内細菌叢の乱れが全身に及ぼす影響を探る
    基盤研究(C)
    2017 - 2019
    長谷部 晃
    文部科学省, Principal investigator, Competitive research funding
  • 口腔常在カンジダは腸管においてカンジダ特異的Tregを誘導するか
    基盤研究(C)
    2014 - 2016
    長谷部 晃
    口腔カンジダ症は、口腔常在性であり加齢にともない検出率が上昇するCandida albicansが主たる要因となることが知られている。しかしながらC. albicansがなぜ口腔内に常在できるのかは依然として不明である。
    我々は、C. albicansが口腔内に常在できるのは経口免疫寛容が誘導されていることによるのではないかと考えた。すなわち、C. albicansが食物や唾液とともに経口的に摂取されることにより、腸管などにおいてC. albicansに特異的な免疫抑制性のT細胞（制御性T細胞、Treg）が誘導され、それによりC. albicansが口腔に定着できるのではないかということである。また、加齢によりC. albicansの検出率が上昇するのは、このC. albicans特異的なTregの数、あるいは割合が増加するのではないかと考えた。
    我々は、まずC. albicansの経口摂取による特異的な免疫抑制の状態を確認するために、C. albicansをマウスに経口的に摂取させ、その後C. albicansを皮下に接種することで特異的抗体の誘導に及ぼす影響を調べた。用いたのは若いあるいは高齢の野生型（WT）ならびにToll-like receptor 2欠損（TLR2KO）C57BL/6マウスである。その結果、WTならびにTLR2KOマウスで大きな違いはなく、若いマウスよりも高齢のマウスにおいて、C. albicansの経口摂取によりC. albicans特異的IgGが有意に強く誘導された。これは経口摂取が、皮下免疫による抗体誘導に対しては抑制的に作用しないということを示している。今後は糞便中のIgAならびに血清中のIgEについても調べ、さらに腸管におけるTregについても調べ、C. albicansの経口摂取が免疫系に及ぼす影響を確認する。
    文部科学省, Principal investigator, Competitive research funding
  • Development of a method to remove mycoplasmas from the contaminated cell cultures using antimicrobial photodynamic therapy
    Grants-in-Aid for Scientific Research
    2011 - 2013
    HASEBE Akira
    Mycoplasmas are one of the most frequent contaminants due to their characteristics in cell cultures. It is required to develop a method to remove mycoplasmas without using antibiotics, because a treatment with antibiotics may induce antibiotic-resistant bacteria. This study attempted to remove cell culture-contaminating Mycoplasma salivarium (Ms) by utilizing antimicrobial photodynamic therapy with a cordless red light emitting diode. Ms-infected human embryonic kidney 293 cells was irradiated with red light emitting diode in the presence of methylene blue as a photosensitizer, after decreasing the number of live Ms by washing with sterilized phosphate-buffered saline. No MS was detected in the contaminated cells by both mycoplasma detection kit and cultivation after antimicrobial photodynamic therapy, demonstrating that antimicrobial photodynamic therapy successfully remove Ms from its contaminated cells without giving damages to the cells.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (C), Hokkaido University, Principal investigator, Competitive research funding, 23592692
  • Activation of regulatory T cells by oral inhabitant bacteria and relationship of their existence and growth of cancer
    Grants-in-Aid for Scientific Research
    2010 - 2012
    SHIBATA Ken-ichiro; HASEBE Akira
    Both wild-type (WT) and lipoprotein-deficient (dLP) strains of oral streptococci, S. mutans and S. gordonii, increased the proliferation of CD4+CD25+Foxp3+ regulatory T cells, but reduced their suppressive activity. However, the presence of lipoprotein was not involved in these activities.WT strain of S. gordonii suppressed the growth of B16 melanoma in C57BL/6 mice, whereas dLP strain did not, suggesting that the presence of lipoprotein plays an important role in the anti-tumor activity. In addition, it was found that NK cells, but not cytolytic T cells, were involved in the anti-tumor acitivity.
    Japan Society for the Promotion of Science, Grant-in-Aid for Scientific Research (B), Hokkaido University, Coinvestigator not use grants, Competitive research funding, 22390352
  • The roles of bacterial lipoproteins on bacterial invasion and on intracellular trafficking in host cells
    Grants-in-Aid for Scientific Research(若手研究(B))
    2009 - 2010
    Akira HASEBE
    To study the roles of bacterial lipoproteins on bacterial invasion to host cells and on the effects on intracellular trafficking in host cells, attempts were made to purify a mycoplasmal lipoprotein, since some mycoplasmas are known to be able to invade into host cells. In this study, a lipoprotein was purified from M. hominis. The 40 kDa-lipoprotein was purified, and its N-terminal amino acid sequence was identical to that of P50 lipoprotein, which had already been reported as an adhesin of M. hominis. Interestingly, this lipoprotein could adhere to THP-1 cells but anti TLR2 antibody faile...
    Ministry of Education, Culture, Sports, Science and Technology, 若手研究(B), 北海道大学, Principal investigator, Competitive research funding, 21791780
  • A crosstalk between Toll-like receptor and C-type lectin
    Grants-in-Aid for Scientific Research(基盤研究(B))
    2007 - 2009
    Kenichiro SHIBATA; Akira HASEBE
    Hosts recognize microbial invasion and then kill them intracellularily. In this study, we demonstrated that the signal mediated by a sensor that recognize bacterial invasion was suppressed by that by phagocytic receptor.
    Ministry of Education, Culture, Sports, Science and Technology, 基盤研究(B), 北海道大学, Coinvestigator not use grants, Competitive research funding, 19390477
  • Studies on molecular mechanism of phagocytosis in innate immune system
    Grants-in-Aid for Scientific Research(若手研究(B))
    2007 - 2008
    Akira HASEBE
    マイコプラズマのリポタンパク質に由来する活性リポペプチドであるFSL-1を用いて、自然免疫において重要な役割を果たすファゴサイトーシスの分子メカニズムについて調べている。2007年度は、FSL-1はマクロファージに取り込まれ、その取り込みはクラスリン依存的であること、ならびにその取り込みはFSL-1の受容体であるTLR2非依存的であること明らかにした。しかしながらFSL-1の取り込みに重要な受容体は不明のままであった。そこで2008年度は、FSL-1の取り込みに重要な受容体を検索し、CD14ならびにCD36が重要であることを明らかにした。これらの詳細なデータは論文にまとめたところであり、国際的な学術雑誌に投稿中である。
    Ministry of Education, Culture, Sports, Science and Technology, 若手研究(B), 北海道大学, Principal investigator, Competitive research funding, 19791337
  • Effects of microbial lipoproteins and lipopeptides on the growthof tumor
    Grants-in-Aid for Scientific Research(基盤研究(C))
    2007 - 2008
    木浦 和人; 柴田 健一郎; 長谷部 晃
    微生物由来物質と腫瘍抗原と一緒に免疫してマウスに腫瘍を接種すると、腫瘍の増殖が著しく抑制され、生存率も著しく伸びた。しかしながら、微生物由来物質を単独、FSL-1 を単独で免疫した場合は、腫瘍の増殖が著しく増強され、生存率も著しく低下した。この相反する活性の原因を細胞レベルで明らかにした。
    Ministry of Education, Culture, Sports, Science and Technology, 基盤研究(C), 北海道大学, Coinvestigator not use grants, Competitive research funding, 19592166
  • 歯周病克服への新たなアプローチを目指して〜歯周病原細菌由来リポタンパク質の研究
    科学研究費補助金(若手研究(B))
    2002 - 2003
    長谷部 晃
    Bacteroides forsythus由来のリポタンパク質(BfLP)の生物活性について、以下のことを明らかにした。● BfLPはヒト正常歯肉線維芽細胞(hGF)にIL-6産生を誘導し、単球・マクロファージ系細胞株THP-1にTNF-αの産生を誘導する。また、Lipopolysaccharideの活性を消失させるポリミキシンBはこの活性に影響を与えない。● BfLP刺激により、hGFならびにTHP-1においてNF-κBが経時的に活性化されている。● BfLPのレセプターとして、自然免疫系のレセプターとして重要であるtoll-like receptor (TLR)のひとつであるTLR2が関与している。● BfLPは最終濃度1μg/ml以下の刺激では炎症性サイトカイン産生を誘導するが、それ以上の濃度による刺激では細胞死を誘導する。● BfLPは最終濃度6μg/mlでhGFに100%、歯肉上皮系細胞KBに80%程度細胞死を誘導する。● BfLPは最終濃度6μg/mlで単球・マクロファージ系細胞株HL-60ならびにTHP-1に細胞死を誘導するが、リンパ球形細胞株MOLT-4には細胞死を誘導しない。● 上記の細胞死はアポトーシスを伴い、それぞれcaspase-8の活性化が確認される。● 歯周病患者・健常者それぞれ10名のBfLPに対する抗体価を比較すると、歯周病患者の平均抗体価は健...
    文部科学省, 若手研究(B), 北海道大学, Principal investigator, Competitive research funding, 14770999
  • 歯肉線維芽細胞にIL-6とIL-8を誘導するマイコプラズマ由来物質の精製と性状
    科学研究費補助金(奨励研究(A))
    1998 - 1999
    長谷部 晃
    〈平成10年度〉ヒト正常歯肉線維芽細胞にInterleukine-6(IL-6)を誘導するMycoplasma salivarium(Ms)由来の物質の性状について新たに得られた知見は以下の通りである。1 Ms由来物質(MsA)はMs細胞内に存在するタンパク性の物質であり、熱処理を行っても活性が30%以上残っている。2 DEAE-sephacelによるイオン交換クロマトグラフィーにより、MsAは、arginine deiminaseとは明らかに異なる物質であるということがわかった。3 さらにCM-sepharose、DEAE-sephacelと、カラムを変えて精製を行った結果、比活性にして30倍以上に達するサンプル(MsA)が得られた。4 MsAのSDS-PAGEを行うと、20.6キロダルトンのメジャーなバンドと2本のかすかなハンド(82.5キロダルトンと40.5キロダルトン)が観察された。5 MaAでTHP-1を刺激したところ、TNF-α、IL-1β、IL-6の産生誘導は見られなかったため、MsAはこれまでに報告されている物質とは異なっている。6 MsAの活性はグラム陰性菌のLPSと異なり、血清の非存在下でも失われることがなかった。〈平成11年度〉ヒト正常歯肉線維芽細胞にIL-6を誘導する物質が、Mycoplasma fermentans(Mf)培養上清中に存在し、その物質...
    文部科学省, 奨励研究(A), 北海道大学, Principal investigator, Competitive research funding, 10770986
  • Physiological and pathological roles of adhesion molecules expressed on gingival fibroblasts in response to oral microbes
    Grants-in-Aid for Scientific Research(基盤研究(C))
    1998 - 1999
    Ken-ichiro SHIBATA; 長谷部 晃; 渡邊 継男
    A lipoprotein with a molecular mass of 44 kDa (Lp44) in Mycopiasma lipoproteins possessed the ICAM-1 expression-inducing activity. The N-terminal amino acid sequence of Lp44 was suggested to be CGDPKH-PKSFTEWVA - and the amino group of the N- terminal cysteine is free. The activity of Lp44 was resistant to proteinase K and sensitive to lipoprotein lipase, suggesting that the lipid moiety, but not the proteinous moiety, of Lp44 is involved in the expression of the activity. The lipid moiety of Lp44 was purified by a reverse-phased HPLC. The activity was eluted at around 90% isopropanol. In o...
    Ministry of Education, Culture, Sports, Science and Technology, 基盤研究(C), 北海道大学, Coinvestigator not use grants, Competitive research funding, 10671762