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2003 Fiscal Year Final Research Report Summary

Periodontal Diseases as a Hypersensitivity Reaction Based on Innate Immune Responses in Periodontal Tissues

Research Project

Project/Area Number 14370576
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field Morphological basic dentistry
Research InstitutionTohoku University

Principal Investigator

TAKADA Haruhiko  Tohoku University, Graduate School of Dentistry, Professor, 大学院・歯学研究科, 教授 (30135743)

Co-Investigator(Kenkyū-buntansha) UEHARA Akiko  Japan Society for the Promotion of Science, Research Fellow (PD), 特別研究員
FUNAYAMA Hitomi  Tohoku University, Graduate School of Dentistry, Research Associate, 大学院・歯学研究科, 助手 (00359530)
SUGAWARA Shunji  Tohoku University, Graduate School of Dentistry, Professor, 大学院・歯学研究科, 教授 (10241639)
TADA Hiroyuki  Japan Society for the Promotion of Science, Research Fellow (PD), 特別研究員
Project Period (FY) 2002 – 2003
KeywordsHuman gingival fibroblasts / Oral epithelial cells / Innate immunity / CD14 / Toll-like receptor / NOD2 / Gingipain / Protease-activated receptor
Research Abstract

We performed studies based on the hypothesis that "in periodontal tissues in which numerous bacteria inhabit and interact with the cells, host defense systems, especially innate immune systems, are activated constitutively, resulting in hypersensitivity-like reactions leading to tissue destruction and periodontal diseases". The major findings were as follows. 1)Innate immune responses of oral epithelial cells : Human oral epithelial cells could not respond to endotoxic lipopolysaccharide [LPS; Toll-like receptor (TLR) 4 ligand], peptidoglycans (PGN; TLR2 ligand), and muramyldipeptide (MDP; intracellular receptor, NOD2 was discovered in the last year), while they responded to some cell-surface components of periodontopathic bacteria. Interferon-γ(IFNγ)-treated human oral epithelial cells responded to various bacterial components to produce inflammatoty cytokines. 2)Innate immune responses of fibroblasts in periodontal tissues : Human gingival fibroblasts carrying membrane CD14 (mCD14) r … More esponded to LPS, while human periodontal ligament fibroblasts carrying much TLR2 but lacking mCD14 could not respond. to LPS, but responded to PGN. IFNγ-treated human gingival. fibroblasts exhibited marked response to-various bacterial components, accompanied by up-regulation of mCD14 and Myd88, which is a common adaptor molecule for TLRs. Gingipains produced by Porphyroinonas gingivalis cleaved mCD14 on human gingival fibroblasts, resulting in hypo-responsiveness to. LPS. 3)Soluble CD14 (sCD 14) in human saliva : Human salivary gland cells, especially parotid gland cells, produced sCD14: The sCD14 concentration in parotid saliva was comparable to that in human serum. Salivary sCD14-augmented the incorporation of Actinobacillus actinomycetemcomitans by oral epithel oral cells, resulting in the enhancement of the innate immune responses of the cells. 4)TLR4 agonistic activity of fungal mannan : Fungal cell-wall mannan, including that from oral Candida albicans, activated human monocytic cells in a CD14-and TLR4-dependent manner. Less

  • Research Products

    (38 results)

All Other

All Publications (38 results)

  • [Publications] Tada H, S Sugawara, E Nemoto, N Takahashi, T Imamura, J Potempa, J Travis, H.Shimauchi, H.Takada: "Proteolysis of CD14 on human gingival fibroblasts by arginine-specific cysteine proteinases from Porphyromonas gingivalis leading to down-regulation of lipopolysaccharide-induced interleukin-8 production."Infection and Immunity. 70-6. 3304-3307 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tada H, E Nemoto, H Shimanchi, T Watanabe, T Mikami, T Masumoto, N Ohno, H Tamura, K Shibata, S Akashi, K Miyake, S Sugawara, H Takada: "Saccharomyces cerevisiae- and Candida albicans-derived mannan induced production of tumor necrosis factor alpha by human monocyses in a CD14- and Toll-likwe receptor 4-dependent manner."Microbiology and Immunology. 46-7. 503-512 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Uehara A, S Sugawara, H Takada: "Priming of human oral epithelial cells by interferon-γ to secrete cytokines in response to lipopolysaccharides, lipoteichoic acids and peptidoglycans."Journal of Medical Microbiology. 51-8. 626-634 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takada H, S Yokoyama, S Ynag: "Enhancement of endotoxin activity by muramyldipeptide"Journal of Endotoxin Research. 8-5. 337-342 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Uehara A, S Sugawara, K.Muramoto, H.Takada: "Activation of human oral epithelial cells by neutrophil proteinase 3 through protease-activated receptor-2."The Journal of Immunology. 169-8. 4594-4603 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takehana A, T Katsuyama, T Yano, Y Oshima, H Takada, T Aigaki, S Kurata: "Overexpression of a pattern-recognition receptor, peptidoglycan-recognition protein-LE, activates imd/relish-mediated antibacterial defense and the prophenoloxidase cascade in Drosophila larvae."Proceedings of the National Academy of Sciences of the United States of America. 99-21. 13705-13710 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Zhao L, Y Ohtaki, K Yamaguchi, M Matsushita, T Fujita, T Yokochi, H Takada, Y Endo: "LPS-induced platelet response and rapid shock in mice : contribution of O-antigen region of LPS and involvement of the lectin pathway of the complement system."Blood. 100-9. 3233-3239 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sugawara S, A Uehara, R Tamai, H Takada: "Innate immune responses in oral mucosa."Journal of Endotoxin Research. 8-6. 465-468 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ohtaki Y, H Shimauchi, T Yokochi, H Takada, Y Endo: "In vivo platelet response to lipopolysaccharide in mice ; proposed method for evaluation new antiplatelet drugs."Thrombosis Research. 108-5.6. 303-309 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Hatakeyama J, R Tamai, A Sugiyama, S Akashi, S Sugawara, H Takada: "Contrasting responses of human gingival and periodontal ligament fibroblasts to bacterial cell-surface components through the CD14/Toll-like receptor system."Oral Microbiology and Immunology. 18-2. 14-23 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Uehara A, S Sugawara, K Watanabe, S Echigo, M Sato, T Yamaguchi, H Takada: "Constitutive expression of a bacterial pattern recognition receptor, CD14, in human salivary glands and secretion as a soluble form in saliva."Clinical and Diagnostic Laboratory Immunology. 10-2. 286-292 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Suzuki M, Shinohara F, Sato K, Taniguchi T, Takada H, Rikiishi H.: "Interleuki-1β converting enzyme subfamily inhibits prevent induction of CD86 molecules by butyrate through a CREB-dependent mechanism in HL60 cells."Immunology. 108-3. 375-383 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Uehara A, Muramoto K, Takada H, S Sugawara: "Neutrophil serine proteases activate human nonepithelial cells to produce inflammatory cytokines through protease-activated receptor 2."The Journal of Immunology. 170-11. 5690-5696 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tamai R, S Sugawara, O Takeuchi, S Akira, H Takada: "Synergistic effects of lipopolysaccharides and interferon-γ in inducing interleukin-8 production in human monocytic THP-1 cells accompanied by up-regulation of CD14, Toll-like receptor 4, MD-2 and MyD88 expression."Journal of Endotoxin Research. 9-3. 145-153 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ozawa A, Tada H, Tamai R, Uehara A, Watanabe K, Yamaguchi T, Shimauchi H, Takada H, Sugawara S.: "Expression of IL-2 receptor β and γ chains by human gingival fibroblasts and up-regulation of adhesion to neutrophils in response to IL-2."Journal of Leukocyte Biology. 74-3. 352-359 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takayama A, Satoh A, Nagai T, Nishimura T, Ikawa K, Matsuyama T, Shimauchi H, Takada H, Sugawara S.: "Augmentation of Actinobacillus actinomycetemcomitans invasion of human oral epithelial cells up-regulation of interleukin-8 production by saliva CD14."Infection and Immunity. 71-10. 5598-5604 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tada H, Sugawara S, Nemoto E, Imamura T, Po-tempa J, Travis J, Shimauchi H, Takada H.: "Proteolysis of ICAM-I on human oral epithelial cells by gingipains."Journal of Dental Research. 82-10. 796-801 (2003)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sato K, Taniguchi T, Suzuki M, Shinohara F, Takada H, Rikiishi H.: "Dual role of NF-κB in apoptosis of THP-1 cells during treatment with etoposide and lipopolysaccharide."Leukemia Research. 28-1. 63-69 (2004)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Ohba M, Shibazaki M, Sasano T, Inoue M, Takada H, Endo Y.: "Platelet responses and anaphylaxis-like shock induced in mice by intravenous injection of whole cells of oral streptococci."Oral Microbiology and Immunology. 19-1. 26-30 (2004)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Tada H, Sugawara S, Nemoto, E, Takahashi N, Imamura T, Potempa J, Travis J, Shimauchi H, Takada H.: "Proteolysis of CD14 on human gingival fibroblasts by arginine-specific cysteine proteinases from Porphyromonas gingivalis leading to down-regulation of lipopolysaccharide-induced interleukin-8 production"Infection and Immunity. 70-6. 3304-3307 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tada H, Nemoto E, Shimauchi H, Watanabe T, Mikami T, Matsumoto T, Ohno N, Tamura H, Shibata K, Akashi S, Miyake K, Sugawara S, Takada H: "Saccharomyces cerevisiae-and Candida albicans-derived mannan induced production of tumor necrosis factor alpha by human monocytes in a CD14-and Toll-like receptor 4-dependent manner"Micirobiology and Immunology. 46-7. 503-512 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Uehara A, Sugawara S, Takada H.: "Priming of human oral epithelial cells by interferon-γ to secrete cytokines in response to lipopolysaccharides, lipoteichoic acids and peptidoglycans"Journal of Medical Microbiology. 51-8. 626-634 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takada H, Yokoyama S, Yang S.: "Enhancement of endotoxin activity by muramyldipeptide"Journal of Endotoxin Research. 8-5. 337-342 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Uehara A, Sugawara S, Muramoto K, Takada H.: "Activation of human oral epithelial cells by neutrophil proteinase 3 through protease-activated treceptor-2"Journal of Immunology. 169-8. 4594-4603 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takehana A, Katsuyama T, Yano T, Oshima Y, Takada H, Aigaki T, Kurata S.: "Overexpression of a pattern-recognition receptor, peptidoglycan-recognition protein-LE, activates imd/relish-mediated antibacterial defense and the prophenoloxidase cascade in Drosophila larvae"Proceedings of the National Academy of Sciences of the United States of America. 99-21. 13705-13710 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Zhao L, Ohtaki Y, Yamaguchi K, Matsushita M, Fujita T, Yokochi T, Takada H, Endo Y.: "LPS-induced platelet response and rapid shock in mice : contribution of O-antigen region of LPS and involvement of the lectin pathway of the complement system"Blood. 100-9. 3233-3239 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sugawara S, Uehara A, Tamai R, Takeda H.: "Innate immune responses in oral mucosa"Journal of Endotoxin Research. 8-6. 465-468 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ohtaki Y, Shimauchi H, Yokochi T, Takada H, Endo, Y.: "In vivo platelet response to lipopolysaccharide in mice : proposed method for evaluating new antiplatelet drugs"Thrombosis Research. 108-5.6. 303-309 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Hatakeyama J, Tamai R, Sugiyama A, Akashi S, Sugawara S, Takada H.: "Contrasting responses of human gingival and periodontal ligament fibroblasts to bacterial cell-surface components through the CD14/Toll-like receptor system"Oral Microbiology Immunology. 18-2. 14-23 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Uehara A, Sugawara S, Watanabe K, Echigo S, Sato M, Yamaguchi T, Takeda H.: "Constitutive expression of a bacterial pattern recognition receptor, CD14, in human salivary glands and secretion as a soluble form in saliva"Clinical and Diagnostic Laboratory Immunology. 10-2. 286-292 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Suzuki M, Shinohara F, Sato K, Taniguchi T, Takeda H, Rikiishi H.: "Interleukin-1β converting enzyme subfamily enhancement of endotoxin activity by butyrate through a CREB-dependent mechanism in HL60 cells"Immunology. 108-3. 375-383 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Uehara A, Muramoto K, Takada H, Sugawara S.: "Neutrophil serine proteinases Activate human non-epithelial cells to produce inflammatory cytokines through protease-activated receptor-2"Journal of Immunology. 170-11. 5690-5696 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tamai R, Sugawara S, Takeuchi O, Akira T, Takada H.: "Synergistic effects of lipopolysaccharide and interferon-γ in inducing interleukin-8 production in human monocytic THP-1 cells is accompanied by up-regulation of CD14, Toll-like receptor 4, MD-2 and MyD88 expression"Journal of Endotoxin Research. 9-3. 145-153 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ozawa A, Tada H, Tamai R, Uehara A, Watanabe K, Yamaguchi T, Shimauchi H, Takada H, Sugawara S.: "Expression of IL-2 receptor β and γ chains by human gingival fibroblasts and up-regulation of adhesion to neutrophils in response to IL-2"Journal of Leukocyte Biology. 74-3. 352-359 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takayama A, Satoh A, Ngai T, Nishimura T, Ikawa K, Matsuyama T, Shimauchi H, Takada H, Sugawara S.: "Augmentation of Actinobacillus actinomycetemcomitans Invasion of Human Oral Epithelial Cells and Up-Regulation of Interleukin-8 Production by Saliva CD14"Infection and Immunity. 71-10. 5598-5604 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Tada H, Sugawara S, Nemoto E, Imamura T, Potempa J, Travis J, Shimauchi H, Takada H.: "Proteolysis of ICAM-1 on human oral epithelial cells by gingipains"Journal of Dental Research. 82-10. 796-801 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sato K, Taniguchi T, Suzuki M, Shinohara F, Takada H, Rikiishi H.: "Dual role of NF-κB in apoptosis of THP-1 cells during treatment with etoposide and lipopolysccharide"Leukemia Research. 28-1. 63-69 (2004)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Ohba M, Shibazaki M, Sasano T, Inoue M, Takada H, Endo Y.: "Platelet responses and anaphylaxis-like shock induced in mice by intravenous injection of whole cells of oral streptococci"Oral Microbiology and Immunology. 19-1. 26-30 (2004)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2005-04-19  

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