Participation of c-fosgene with pathogenesis of periodontitis

Research Project

Project/Area Number	08457510
Research Category	Grant-in-Aid for Scientific Research (B)
Allocation Type	Single-year Grants
Section	一般
Research Field	Conservative dentistry
Research Institution	Showa University
Principal Investigator	HASEGAWA Kohoji Showa University, Dental school Professor, 歯学部, 教授 (70014024)
Co-Investigator(Kenkyū-buntansha)	SHIONOME Manabu Showa University, Dental school Assistant, 歯学部, 助手 (50245809) MIYAGAWA Yasushi Showa University, Dental school Lecture, 歯学部, 講師 (90219775) KOBAYASHI Makoto Showa University, Dental school Lecture, 歯学部, 講師 (80186767)
Project Period (FY)	1996 – 1998
Project Status	Completed (Fiscal Year 1998)
Budget Amount *help	¥6,100,000 (Direct Cost: ¥6,100,000) Fiscal Year 1998: ¥1,400,000 (Direct Cost: ¥1,400,000) Fiscal Year 1997: ¥2,400,000 (Direct Cost: ¥2,400,000) Fiscal Year 1996: ¥2,300,000 (Direct Cost: ¥2,300,000)
Keywords	periodontitis / c-fosgene / human gingibal fiibroblasto / interleukin-1 / cell growth / intercellular 1L-1αproduction / prostaglandin EィイD22ィエD2 production / 歯周病 / C-fos / 細胞増殖 / プロスタグランディンE_2 / メタプロテアーゼ / c-fos / PGE_2産生 / メタロプロテアーゼ産生 / c-fos遺伝子発現 / 歯周病病態形成 / プロスタグランジンE_2 / メタロプロテアーゼ
Research Abstract	Previous reports demonstrated that c-fos gene participates with cell growth and differentiation, and this may play an important role in intracellular signaling cascade of inflammatory cytokines and lipopolisaccharide. Interleukin-1 (IL-1) stimulates local inflammation through enhancement of inflammatory factors' production and induces destraction of periodontal tissues. The purpose of this study was to clarify a participation of c-fos gene with pahthogenesis of periodontitis. In this study, we investigated that the participation of c-fos gene with IL-1-induced cell growth and production of intracellular IL-1α and prostaglandin EィイD22ィエD2(PGEィイD22ィエD2) in human gingival fibroblasts (HGF). Results obtained as follows : (1) IL-1β stimulated c-fos mRNA expression more rapidly than expression of IL-1α, cyclooxygenase-2(COX-2) and cytosolic phospholipase AィイD22ィエD2 (cPLAィイD22ィエD2) mRNA. (2) IL-1β-induced cell growth, expression of IL-1α, COX-2 and cPLAィイD22ィエD2 mRNA and synthesis of intracellular IL-1α and PGEィイD22ィエD2 were partially inhibited by co-treatment with c-fos antisense ODN. (3) Co-treatment with curcumin, a inhibitor of activating protein-1 (AP-1), suppressed IL-1β-induced IL-1α, COX-2 and cPLAィイD22ィエD2 mRNA expression and intracellular IL-1α and PGEィイD22ィエD2 synthesis. These results demonstrated that c-fos gene may play a principal role in cell growth and production of intracellular IL-1α and PGEィイD22ィエD2 in human gingival fibroblasts stimulated with IL-1β, and these suggested a participation of c-fos gene with pahthogenesis of periodontitis.