| Project/Area Number |
07672073
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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 |
Conservative dentistry
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| Research Institution | Tokyo Medical & Dental University |
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Principal Investigator |
NOGUCHI Kazuyuki Tokyo Medical & Dental University, Faculty of Dentistry, Assistant, 歯学部, 助手 (90218298)
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| Co-Investigator(Kenkyū-buntansha) |
HIMI Toshiyuki Tokyo Medical & Dental University, Graduate School, Assistant, 歯学研究科, 助手 (30222243)
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| Project Period (FY) |
1995 – 1997
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| Project Status |
Completed (Fiscal Year 1997)
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| Budget Amount *help |
¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1997: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1996: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1995: ¥700,000 (Direct Cost: ¥700,000)
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| Keywords | periodontal disease / gingival fibroblast / periodontal ligament cells / prostaglandin E_2 / cyclooxygenase-2 / LPS / interleukin-1 / Th2 cytokine / IL-1β / MMP-1 / IL-x / IL-13 / EPレセプター / IL-1α / IL-4 / PGE_2 / COX-2 / 単球 / シクロオキシゲナーゼ-ス / インターロイキン-1β / リポポリサッカライド |
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| Research Abstract |
1. The involvement of cycloocygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) in prostaglandin E_2 (PGE_2) production by human gingival fibroblasts (HGF) stimulated with periodontpathic bacteria was investigated. Lipopolysaccharides isolated from Porphyromonas gingivalis (P.gingivalis) and Actinobacillus actinomycetemcomitants (A.actinomycetemcomitans) were prepared. The LPS preparations produced PGE_2 in a dose- and time-dependent manner. P.gingivalis-LPS was a more potent stimulator than A.actinomycetemcomitans-LPS.Treatment of the cells with NS-398, a selective COX-inhibitor, completely suppresed PGE_2 production. Immunohistochemical staining of COX-2 showed that COX-2 protein expression was increased 24 h after P.gingivalis-LPS.The COX-2 expression was inhibted by treatment with tyrosine kinase inhibitors, which suggested that tyrosine kinase was involved in COX-2 expression.
The effect of Th2 cytokines, interleukin (IL)-4 and -13, on PGE_2 production by IL-1alpha-stimulated periodontal ligament (PDL) cells was studied. Treatment of the IL-1alpha-cells with IL-4 and -13 inhibited PGE_2 production in a dose-dependent manner. IL-4 and -13 suppressed COX-2 mRNA expression. It was suggested that IL-4 and -13 regulate PGE_2 production by IL-1alpha-stimulatedPDL cells, through COX-2 expression.
3. The effect of PGE_2 on matrix metalloproteinase-1 (MMP-1) by IL-1beta-stimulated HGF was investigated. Treatment of the cells with NS-398 enhanced MMP-1 generation and exogenous addition of PEG_2 also inhibited MMP-1 production. The data suggested that PGE_2 regulated MMP-1 production by IL-1beta-stimulated HGF.Treatment of the cells with IL-4 and -13 enhanced MMP-1 production, by inhibiting PGE_2 production.
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