Co-Investigator(Kenkyū-buntansha) |
NEMOTO Eiji Tohoku University, Graduate School of Dentistry, Research Associate, 大学院・歯学研究科, 助手 (40292221)
SUGAWARA Shunji Tohoku University, Graduate School of Dentistry, Research Associate, 大学院・歯学研究科, 助手 (10241639)
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Budget Amount *help |
¥14,300,000 (Direct Cost: ¥14,300,000)
Fiscal Year 2001: ¥6,800,000 (Direct Cost: ¥6,800,000)
Fiscal Year 2000: ¥7,500,000 (Direct Cost: ¥7,500,000)
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Research Abstract |
Toll-like receptors (TLR) are involved in the ability of the host innate immune system to recognize microbial patterns. We studied recognition of various bacterial components by the host innate immune system, especially cells in periodontal tissues, in relation to the pathogenesis of mucosal diseases in the oral cavity. We obtained the following findings, (l) Three cysteine proteases, gingipains, from periodontopathic Porphyromonas gingivalis cleaved membrane C 14 (mCD14) on human monocytes, leading to lipopolysaccharide (LPS) hyporesponsiveness of the cells. (2) Human leukocyte elastase cleaved mCD14 on human gingival fibroblasts (HGF), resulting in LPS hyporesponsiveness of the cells. (3) Gingival epithelial cells that lacked mCD14 did not respond to LPS, peptidoglycan (PGN), muramyldipeptide (MDP) which is a critical moiety of PGN, or lipoteichoic acids (LTA) from gram-positive bacteria even in the presence of soluble CD14 (sCD14) in contrast to the response of colonic epithelial cells. (4) Water-soluble PGN, SEPS, prepared from Staphylococcus epidermidis activated cells in a TLR2-dependent manner. When the glycan chain of SEPS was cleaved enzymatically, the TLR2-dependent activity of SEPS disappeared, and MDP was also inactive in this respect. (5) MDP activated human monocytic cells in a CD14- and TLR2-independent manner and up-regulated expression of MyD88, resulting in synergistic activation of the cells in combination with LPS or LTA, both of which are TLR4-dependent activators. (6) Interferon-γ primed HGF to increase response to LPS through up-regulation of mCD14 and MyD88 mRNA expression. Further studies are in progress in our laboratory to identify interactions between bacterial components and the host innate immune system in relation to pathogenesis of periodontal diseases.
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