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2000 Fiscal Year Final Research Report Summary

Analysis of endotoxin antagonism of lipoteichoic acids from oral streptococci

Research Project

Project/Area Number 11671796
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, Assistant Professor, 大学院・歯学研究科, 助手 (10241639)

Co-Investigator(Kenkyū-buntansha) TAKADA Haruhiko  Tohoku University, Graduate School of Dentistry, Professor, 大学院・歯学研究科, 教授 (30135743)
Project Period (FY) 1999 – 2000
Keywordsoral streptococci / lipoteichoic acids / endotoxin / antagonist / CD14 / Toll-like receptors / periodontitis
Research Abstract

1. Lipoteichoic acids (LTAs) of oral streptococci, Streptococcus sanguis and Streptococcus mutans, was shown to antagonize the activity of inflammatory cytokine production from CD14-positive human gingival fibroblasts (HGF) and human monocytes in response to endotoxin (LPS, lipopolysaccharide) and its active moiety, synthetic lipid A.
2. In addition to CD14 as a bacterial component receptor, Toll-like receptors (TLRs) transduce signals of the components into the cells. LTAs of other bacteria and LPS activated murine macrophages in a CD14/TLR2-and CD14/TLR4-dependent pathway, respectively, using gene knockout mice.
3. An well known LPS antagonist, a synthetic lipid A precursor (LA-14-PP) inhibited the function of CD14/TLR4 ligand (LPS) as well as CD14/TLR2 ligand (LTA) in human system, suggesting that CD14 is critically involved in the antagonism.
4. Binding of oral streptococcal LTAs to human monocytes was inhibited by anti-CD14 antibody and the LTAs binded to recombinant CD14 in a native-polyacrylamide gel electrophoresis, showing that the antagonism of the LTAs is mediated by competing with cell surface CD14.
5. Periodontal pathogenic Porphyromonas gingivalis cysteine proteinase (gingipain) and human neutrophil serine proteinase (elastase) preferentially proteolysed CD14 on human monocytes and HGF, resulting in down-modulation of LPS responsiveness of the cells.

  • Research Products

    (20 results)

All Other

All Publications (20 results)

  • [Publications] Sugawara,S.: "Lipoteichoic acid acts as an antagonist and an agonist of lipopolysaccharide in human gingival fibroblasts and monocytes in a CD14-dependent manner."Infection and Immunity. 67. 1623-1632 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 菅原俊二: "歯肉線維芽細胞のCD14発現の多様性とその機能."歯科基礎医学会雑誌. 41. 98-107 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Endo,Y.: "Enhancement by galactosamine of lipopolysaccharide(LPS)-induced tumour necrosis factor production and lethality : its suppression by LPS pretreatment."British Journal of Pharmacology. 128. 5-12 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Takeuchi,O.: "Differential roles of TLR2 and TLR4 in recognition of Gram-negative and gram-positive bacterial cell wall components"Immunity. 11. 443-451 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Kai,K.: "Lipopolysaccharide-dependent down-regulation of CD27 expression on T cells activated with superantigen."Immunology. 98. 289-295 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nemoto,E.: "Increase of CD26/dipeptidyl peptidase IV expression on human gingival fibroblasts upon stimulation with cytokines and bacterial components."Infection and Immunity. 67. 6225-6233 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 菅原俊二: "歯学情報 菌体表層成分の認識機構と歯周疾患."東北大学歯学雑誌. 18. 187 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sugawara,S.: "Proteolysis of human monocyte CD14 by cysteine proteinases(gingipains)from Porphyromonas gingivalis leading to lipopolysaccharide hyporesponsiveness."The Journal of Immunology. 165. 411-418 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Nemoto,E.: "Cleavage of CD14 on human gingival fibroblasts cocultured with activated neutrophils is mediated by human leukocyte elastase resulting in down-regulation of lipopolysaccharide-induced IL-8 production."The Journal of Immunology. 165. 5807-5813 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 根本英二: "ヒト歯肉線維芽細胞膜上のCD26/dipeptidyl peptidase IV-サイトカインおよび菌体成分による発現増強."炎症. 20. 596-602 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Sugawara, S.: "Lipoteichoic acid acts as an antagonist and an agonist of lipopolysaccharide on human gingival fibroblasts and monocytes in a CD14-dependent manner."Infect.Immun.. 67-4. 1623-1632 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sugawara, S.: "Heterogeneous expression of CD14 by human gingival fibroblasts and function of the CD14."Jpn. J.Oral Biol.. 41-2. 98-107 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Endo, Y.: "Enhancement by galactosamine of lipopolysaccharide (LPS)-induced tumour necrosis factor production and lethality : its suppression by LPS pretreatment."Br. J.Pharmacol.. 128-1. 5-12 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Takeuchi, O.: "Differential roles of TLR2 and TLR4 in recognition of gram-negative and gram-positive bacterial cell wall components."Immunity. 11-4. 443-451 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Kai, K.: "Lipopolysaccharide-dependent down-regulation of CD27 expression on T cells activated with superantigen."Immunology. 98-2. 289-295 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nemoto, E.: "Increase of CD26/dipeptidyl peptidase IV expression on human gingival fibroblasts upon stimulation with cytokines and bacterial components."Infect Immun.. 67-12. 6225-6233 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sugawara, S.: "Molecular mechanism of bacterial cell surface component recognition and periodontitis."Tohoku Univ. Dent. J.. 18-2. 187 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Sugawara, S.: "Proteolysis of human monocyte CD14 by cysteine proteinases (gingipains) from Porphyromonas gingivalis leading to lipopolysaccharide hyporesponsiveness."J.Immunol.. 165-1. 411-418 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nemoto, E.: "Cleavage of CD14 on human gingival fibroblasts cocultured with activated neutrophils is mediated by human leukocyte elastase resulting in down- regulation of lipopolysaccharide-induced IL-8 production."J.Immunol.. 165-10. 5807-5813 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Nemoto, E.: "CD26/dipeptidyl peptidase IV on human gingival fibroblasts-increase of the expression upon stimulation with cytokines and bacterial components-."Jpn. J.Inflammation.. 20-5. 596-602 (2000)

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

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Published: 2002-03-26  

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