| Project/Area Number |
17592166
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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 |
Periodontal dentistry
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| Research Institution | Nihon University |
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Principal Investigator |
NAKAO Sumi Nihon University, School of Dentistry at Matsudo, Research Assistant(Full-Time), 松戸歯学部, 助手 (20102577)
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| Co-Investigator(Kenkyū-buntansha) |
OGATA Yorimasa Nihon University, School of Dentistry at Matsudo, Professor, 松戸歯学部, 教授 (90204065)
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| Project Period (FY) |
2005 – 2006
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| Project Status |
Completed (Fiscal Year 2006)
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| Budget Amount *help |
¥2,200,000 (Direct Cost: ¥2,200,000)
Fiscal Year 2006: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2005: ¥1,300,000 (Direct Cost: ¥1,300,000)
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| Keywords | human gingival fibroblasts / inflammation / calcineurin / cyclosporin A / prostaglandin E2 / cyclooxygenase / シクロオキシゲナーゼー2 / 転写因子 / プロスタグランジンE2 / サクロスポリンA |
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| Research Abstract |
Calcineurin is a calcium-activated serine/threonine phosphatase critical to a number of developmental processes in the immune systems. The role of Calcineurin in the immune response is underscored by the calcineurin inhibitors, such as cyclosporin A and FK506. We have previously demonstrated that pro-inflammatory cytokines, IL-16 and TNF-a induced PGE_2 release in human gingival fibroblasts. In this research project, we investigated whether Calcineurin inhibitors affect PGE_2 synthesis in human gingival fibroblasts. We analyzed the effects of cyclosporin A and FK506 on the PGE_2 release and the expression of cyclooxygenase-2 mRNA.
Cyclosporin A induced cyclooxygenase-2 expression as well as prostaglandin E_2 release. This induction was more prominent when human gingival fibroblasts were treated with IL-16. Cyclosprin A induced PGE2 release in dose-and time-dependent manner, and reached a maximum at 10 μM for 24h. Cyclosporin A and FK506 partially increased IL-18-mediated PGE_2 release. Moreover, in the gingival fibroblasts pretreatment with IL-1β, cyclosporin A augmented bradykinin-stimulated PGE_2 release. RT-PCR analysis revealed that cyclosporin A increased the expression of cyclooxygenase-2 mRNA. The simultaneous treatment with cyclosporin A and IL-16 resulted in increased the expression of cyclooxygenase-2 mRNA compared to cells with IL-1β alone. To confirm the RT-PCR results, cyclooxygenase transcript levels were measured by quantitative real time RT-PCR. These real time RT-PCR data supported the RT-PCR results, confirming that cyclooxygenase-2 mRNA was up-regulated by cyclosporin A. Cyclosporin A could acts as an inflammatory mediator, likely by the induction of cyclooxygenase-2-mediated PGE_2 formation in human gingival fibroblasts. Taken together, our data suggest that induction of cyclooxygenase-2 and PGE_2 synthesis are enhanced by cyclosporine A where they may participate in cyclosporin A-induced gingival overgrowth.
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