| Project/Area Number |
11671796
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Morphological basic dentistry
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| Research Institution | Tohoku University |
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Principal Investigator |
SUGAWARA Shunji Tohoku University, Graduate School of Dentistry, Assistant Professor, 大学院・歯学研究科, 助手 (10241639)
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| Co-Investigator(Kenkyū-buntansha) |
TAKADA Haruhiko Tohoku University, Graduate School of Dentistry, Professor, 大学院・歯学研究科, 教授 (30135743)
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| Project Period (FY) |
1999 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥3,900,000 (Direct Cost: ¥3,900,000)
Fiscal Year 2000: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1999: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | oral streptococci / lipoteichoic acids / endotoxin / antagonist / CD14 / Toll-like receptors / periodontitis |
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| 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.
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