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Regulation of oral mucosal immunity in human oral epithelial cells and periodontitis

Research Project

Project/Area Number 13671894
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

SUGAWARA Shunji  Tohoku University, Graduate School of Dentistry, Professor, 大学院・歯学研究科, 教授 (10241639)

Co-Investigator(Kenkyū-buntansha) NEMOTO Eiji  Tohoku University, Graduate School of Dentistry, Assistant Professor, 大学院・歯学研究科, 助手 (40292221)
TAKADA Haruhiko  Tohoku University, Graduate School of Dentistry, Professor, 大学院・歯学研究科, 教授 (30135743)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2001: ¥1,800,000 (Direct Cost: ¥1,800,000)
Keywordsoral epithelial cells / mucosal immunity / cytokines / fibroblasts / saliva / innate immunity / neutrophil proteinases / periodontitis / プロテアーゼ活性化受容体 / 菌体成分
Research Abstract

1. Oral epithelial cells constitutively express precursor form of interleukin-18 (IL-18) in the cells. Bioactive IL-18 was produced from the cells on costimulation with neutrophil serine proteinase, proteinase 3 (PR3), and Iipopolysaccharide (LPS) after interferon-γ (IFN-γ)-priming. PR3 was found to activate oral epithelial cells through G protein-coupled protease-activated receptor-2.
2. Oral epithelial cells do not express a bacterial pattern recognition receptor, CD 14, and express Toll-like receptors (TLRs)/MD-2/MyD88 system, which is critical in innate immune recognition. However, the cells are refractory to bacterial components even in the presence of soluble CD14, The cells are able to respond to components from black-pigmented bacteria (BPB). The cells acquire responsiveness to many bacterial components after priming with IFN-γ.
3. Nonendotoxic glycoprotein from BPB activates host cells in a CD14- and TLR2-dependent manner.
4. CD14-expreswsing human gingival fibroblasts (HGF) have the same property with oral epithelial cells. Human periodontal ligament fibroblasts (HPLF) express TLR2 more strongly than HGF. HGF mainly respond to Gram-negative, and HPLF mainly respond to Gram-positive bacterial components, respectively. Cysteine proteinases (gingipains) from periodontopafhic bacteria degrade CD14 on HGF, consequently, suppress CD14-dependent responsiveness to bacterial components.
5. Human salivary glands constitutively express CD14 and secrete as a soluble form in saliva.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (45 results)

All Other

All Publications (45 results)

  • [Publications] Yang, S.: "Micrococcus luteus teichuronic acids activate human and murine monocytic cells in a CD14-and Toll-like receptor 4-dependent manner"Infect. Immun.. 69. 2025-2030 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yang, S.: "Synergistic effect of muramyldipeptide with lipopolysaccharide or lipoteichoic acid to induce inflammatory cytokines in human monocytic cells in culture"Infect. Immun.. 69. 2045-2053 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sugawara, S.: "Monocytic cell activation by non-endotoxic glycoprotein from Prevotella intermedia ATCC 25611 is mediated by Toll-like receptor 2"Infect. Immun.. 69. 4951-4957 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Uehara, A.: "Contrasting responses of human gingival and colonic epithelial cells to lipopolysaccharides, lipoteichoic acids and peptidoglycans in the presence of soluble CD14"Med. Microbiol. Immunol.. 189. 185-192 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sugawara, S.: "Neutrophil proteinase 3-mediated bioactive IL-18 secretion by human oral epithelial cells"J. Immunol.. 167. 6568-6575 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sugiyama, A.: "Activation of human gingival epithelial cells by cell-surface components of black-pigmented bacteria : augmentation of production of interleukin-8, granulocyte colony-stimulation factor and granulocyte-macrophage colony-stimulating factor and expression of intercellular adhesion molecule 1"J. Med. Microbiol.. 51. 27-33 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tamai, R.: "Human gingival CD14^+ fibroblasts primed with gamma interferon increase production of interleukin-8 in response to lipopolysaccharide through up-regulation of membrane CD14 and MyD88 mRNA expression"Infect. Immun.. 70. 1272-1278 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tada, 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"Infect. Immun.. 70. 3304-3307 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tada, H.: "Saccharomyces cerevisiae-and Candida albicans-derived mannan induced production of tumor necrosis factor alpha by human monocytes in a CD14-and Toll-like receptor4-dependent manner"Microbiol. Immunol.. 46. 503-512 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Uehara, A.: "Priming of human oral epithelial cells by interferon-γ to secrete cytokines in response to lipopolysaccharides, lipoteichoic acids and peptidoglycans"J. Med. Microbiol.. 51. 626-634 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Uehara, A.: "Activation of human oral epithelial cells by neutrophil proteinase 3 through protease-activated receptor-2"J. Immunol.. 169. 4594-4603 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sugawara, S.: "Innate immune responses in oral mucosa"J. Endotoxin Res.. 8. 465-468 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hatakeyama, J.: "Contrasting responses of human gingival and periodontal ligament fibroblasts to bacterial cell-surface components through CD14/Toll-like receptor system"Oral Microbiol. Immunol.. 18. 14-23 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Uehara, A.: "Constitutive expression of a bacterial pattern recognition receptor, CD14, in human salivary glands and secretion as a soluble form in saliva"Clin. Diagn. Lab. Immunol.. 10. 286-292 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tamai, R.: "Synergistic effect of lipopolysaccharide and interferon-γ to induce interleukin-8 production in human monocytic THP-1 cells through up-regulation of CD14, Toll-like receptor4, MD-2 and MyD88 expression"J. Endotoxin Res.. 9(印刷中). (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yane,S., S.Sugawara, T.Monodane, M.Nishijima, Y.Adachi, S.Akashi, K.Miyake, S.Hase, R.Takada: "Micrococcus luteus teichuronic acids activate human and murine monocytic cells in a GDI 4- and Toll-like receptor 4-dependent manner"Infect. Immun.. 69-4. 2025-2030 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yang,S., R.Tamai, S.Akashi, O.Takeuchi, S.Akira, S.Sugawara, H.Takada: "Synergistic effect of muramyldipeptide -with Hpopolysaccharide or lipoteichoic acid to induce inflammatory cytokines in human monocytic cells in culture"Infect. Immun.. 69-4. 2045-2053 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Uehara,A., S.Sugawara, R.Tamai, H.Takada: "Contrasting responses of human gjngival and colonic epithelial cells to lipopolysaccharides, lipoteichoic acids and peptidoglyeans in the presence of soluble CD14"Med. Microbiol, Inimunol.. 189-4. 185-192 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sugawgr,S., S.Yang, K.Iki, J.Hatakeyama, R.Tamai, O.Takeuchi, S.Akashi, T.Espevik, S.Akira, H.Takada: "Monocytic cell activation by nonendotoxic glycoprotein from Prevotella intermedia ATCC 25611 is mediated by Toll-like receptor 2"Infect. Immun.. 69-8. 4951-4957 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sugawara,S., A.Uehara, T.Nochi, T.Yamaguchi, H.Ueda, K.Hanzawa, A.Sugiyama, K.Kumagai, H.Okamura, H.Takada: "Neutrophil proteinase 3 mediated induction of bioactive IL-18 secretion by human oral epithelial cells"J. Immunol.. 167-11. 6568-6575 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sugiyama,A., A.Uehara, K.Iki, K.Matsushita, R.Nakamura, T.Ogawa, S.Sugawara, H.Takada: "Activation of human gingival epithelial cells by cellsurface components of black-pigmented bacteria: augmentation of production of interleukin-8, granulocyte colonystimulation factor and granulocyte-macrophage colony-stimulating factor and expression of intercellular adhesion molecule 1"J. Med. Microbiol.. 51-1. 27-33 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tamai,R., T.Sakuta, K.Matsushita, M.Torii, O.Takeuchi, S.Akira, S.Akashi, T.Espevik, S.Sugawara, H.Takada: "Human gingival CD14^+ fibroblasts primed with gamma interferon increase production of interIeukin-8 in response to lipopolysaccharide through up-regulation of membrane CD14 and MyD88 mRNA expression"Infect Immun.. 70-3. 1272-1278 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tada,H., S.Sueawara, E.Nemoto, N.Takahashi, T.Imamura, J.Potempa, J.Travis, R.Shimauchi, H.Takada: "Proteolysis of CD14 on human gingival. fibroblasts by arginine-specific cysteine proteinases from Porphyromonas gingivalis leadinjg to down-regulation of lipopoiysaccharide-induced interleukin-8 production"Infect. Immun.. 70-6. 3304-3307 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tada,H., E.Nemoto, H.Shimauchi, T.Watanabe, T.Mikami, T.Matsumoto, 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 monocytes in a CD14- and Toll-like receptor 4-dependent manner"Microbiol. Immunol,. 46-7. 503-512 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [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"J. Med. Microbiol.. 51-8. 626-634 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Uehara,A., S.Sugawara, K.Muramoto, H.Takada: "Activation of human oral epithelial, cells by neutrophil proteinase 3 through prptease-activated receptor-2"J. Immunol.. 169-8. 4594-4603 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Sugawara,S., A.Uehara, R.Tamai, R.Takada: "Proceedings. lnnate immune responses in oral mucosa"J. Endotoxin Res.. 8-6. 465-468 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [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 Microbiol. Immunol.. 18-1. 14-23 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [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"Clin. Diagn. Lab. Immunol.. 10-2. 286-292 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tamai,R., S.Sugawara, O.Takeuchi, S.Akira, R.Takada: "Synergistic effect of lipopoiysaccharide and interferon-γ to induce interleukin-8 production in human monocytic THP-1 cells through up-regulation of CD14, Toll-like receptor 4, MD-2 and MyD88 expression"J. Endotoxin Res.. 9-2. (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Tamai, R.: "Human gingival CD14^+ fibroblasts primed with gamma interferon increase production of interleukin-8 in response to lipopolysaccharide through up-regulation of membrane CD14 and MyD88 mRNA expression"Infect.Immun.. 70・3. 1272-1278 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Tada, 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"Infect.Immun.. 70・6. 3304-3307 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Tada, 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"Microbiol.Immunol.. 46・7. 503-512 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Uehara, A.: "Priming of human oral epithelial cells by interferon-γ to secrete cytokines in response to lipopolysaccharides, lipoteichoic acids and peptidoglycans"J.Med.Microbiol.. 51・8. 626-634 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Uehara, A.: "Activation of human oral epithelial cells by neutrophil proteinase 3 through protease-activated receptor-2"J.Immunol.. 169.8. 4594-4603 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Sugawara, S.: "Innate immune responses in oral mucosa"J.Endotoxin Res.. 8・6. 465-468 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hatakeyama, J.: "Contrasting responses of human gingival and periodontal ligament fibroblasts to bacterial cell-surface components through CD14/Toll-like receptor system"Oral Microbiol.Immunol.. 18・1. 14-23 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Uehara, A.: "Constitutive expression of a bacterial pattern recognition receptor, CD14, in human salivary glands and secretion as a soluble form in saliva"Clin.Diagn.Lab.Immunol.. 10・2(印刷中). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Tamai, R.: "Synergistic effect of lipopolysaccharide and interferon-γ to induce interleukin-8 production in human monocytic THP-1 cells through up-regulation of CD14, Toll-like receptor 4, MD-2 and MyD88 expression"J. Endotoxin Res.. 9(印刷中). (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yang, S.: "Micrococcus luteus teichuronic acids activate human and murine monocyclic cells in a CD14-and Toll-like receptor 4-dependent manner"Infection and Immunity. 69.4. 2025-2030 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yang, S.: "Synergistic effect of muramyldipeptide with lipopolysaccharide or lipoteichoic acid to induce inflammatory cytokines in human monocytic cells in culture"Infection and Immunity. 69.4. 2045-2053 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Sugawara, S.: "Monocytic cells activation by non-endotoxic glycoprotein from Prevotella intermedia ATCC 25611 is mediated by Toll-like receptor 2"Infection and Immunity. 69.8. 4951-4957 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Uehara, A.: "Contrasting responses of human gingival and colonic epithelial cells to lipopolysaccharides, lipoteichoic acids and peptidoglycans in the presence of soluble CD14"Medical Microbiology and Immunology. 189.4. 185-192 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Sugawara, S.: "Neutrophil proteinase 3-mediated bioactive IL-18 secretion by human oral epithelial cells"The Journal of Immunology. 167.11. 6568-6575 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Sugiyama, A.: "Activation of human gingival epithelial cells by cell-surface components of black-pigmented bacteria : augmentation of production of interleukin-8,granulocyte colony-stimulating factor and granulocyte-macrophage colony-stimulating factor and expression of intercellular adhesion molecule 1"Journal of Medical Microbiology. 51.1. 27-33 (2002)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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