| Budget Amount *help |
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2000: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1999: ¥2,400,000 (Direct Cost: ¥2,400,000)
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| Research Abstract |
It is thought that occlusal trauma and dental plaque synergistically contribute to the rapid progression of periodontitis, but we have little information about the underlying mechanism. In this study, I examine the effects of cyclic-stretch force and lipopolysaccharide (LPS) from periodontopathic bacteria on expressions of proinflammatory cytokines in human periodontal ligament cell (HPLC) cultures. Interleukin (IL)-6, IL-8, granulocyte colony stimulating factor (G-CSF), and macrophage colony stimulating factor (M-CSF), and vascular endothelial growth factor (VEGF) were produced by cyclic-stretch force in HPLC cultures. When Prevotella intermedia LPS added to the HPLC cultures simultaneously with or prior to the stimulation with cyclic-stretch force. IL-1α was strongly produced in the HPLC cultures. The productions of IL-6, IL-8, and VEGF were enhanced by the costimulation with cyclic-stretch force and P.intermedia LPS.On the other hand, M-CSF production in HPLC cultures decreased by t
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he costimulation. To clarify molecular mechanism of the enhancement of the induction, we examined expression of CD14, which is a LPS receptor, on stretched HPLC.Although CD14 mRNA was not expressed in non-stretched HPLC, the expression was strongly induced by cyclic-stretch force for 4-8 h in HPLC.Productions of membrane CD14 and soluble CD14 were enhanced by the cyclic-stretch force for 24 h on the surface of and in the supernatants of HPLC respectively. IL-6 production was observed even in the supernatants of stretched and non-stretched HPLC, but the production was enhanced upon serial stimulation with stretch force and P.intermedia LPS on HPLC.The protein kinase C (PKC) inhibitor H7 blocked the expression of CD14 mRNA in stretched HPLC, H7 and the anti-CD14 monoclonal antibody MY4 also suppressed the enhancement of IL-6 production in the HPLC cultures upon serial stimutation with stretch force and P.intermedia LPS.The consensus sequence of shear stress-responsive element (SSRE) was found in the 5' flanking region of the CD14 gene. In addition. a DNA probe which contained the consensus sequence of SSRE bound to nuclear extracts from stretched HPLC but not from non-stretched HPLC.These results suggest that cyclic-stretch force induces CD14 expression in HPLC through PKC activation and that SSRE is associated with the expression. In addition, the expression of CD14 may increase the sensitivity of HPLC to LPS. Less
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