| Project/Area Number |
11470461
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 | Osaka University |
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Principal Investigator |
MURAKAMI Shinya Graduate School of Dentistry, Osaka University, Professor, 歯学研究科, 教授 (70239490)
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| Co-Investigator(Kenkyū-buntansha) |
IKEZAWA Kazuhiko Graduate School of Dentistry, Osaka University, Research Associate, 大学院・歯学研究科, 助手 (80294114)
SAHO Teruyuki Dental Hospital, Osaka University, Research Associate, 歯学部・附属病院, 助手 (10263295)
SHIMABUKURO Yoshio Dental Hospital, Osaka University, Assistant Professor, 歯学部・附属病院, 講師 (50231361)
NOZAKI Takenori Graduate School of Dentistry, Osaka University, Research Associate, 大学院・歯学研究科, 助手 (30263304)
岡田 宏 大阪大学, 大学院・歯学研究科, 教授 (40038865)
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| Project Period (FY) |
1999 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥14,400,000 (Direct Cost: ¥14,400,000)
Fiscal Year 2001: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2000: ¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1999: ¥9,400,000 (Direct Cost: ¥9,400,000)
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| Keywords | Periodontal Disease / Adenosine / Gingival fibroblast / Gingival epithelial cell / Inflammatory cytokine / Nitric oxide / Hyaluronan / Adhesion molecule / アデノシンレセプターアゴニスト / 歯周組織 / iNOS / サイトカイン / IL-6 / 細胞外基質 |
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| Research Abstract |
Several lines of evidence have demonstrated that adenosine, an endogenous nucleoside, can modulate the various functions of cells involved in inflammatory responses. In this study, we investigated the effects of adenosine on various functions of resident cells in periodontal tissues. We demonstrated that human gingival fibroblasts (HGF) expressed mRNA of adenosine receptor subtype A1, A2a, and A2b but not A3. Stimulation of HGF with adenosine or adenosine receptor agonists induced IL-6 and IL-8 production. It was also revealed that CAMP, PKA, PKC and PLC were involved in the intracellular signal transduction via adenosine receptors on HGF. In addition, the adenosine stimulation also upregulated mRNA expression of hyaluronan synthase in HGF. On the other hand, adenosine stimulation downregulated the IL-1β-induced ICAM-1 egression on HGF, that resulted in the inhibition of LFA-1-dependent lymphocyte adhesion to HGF. We also demonstrated that human gingival epithelial cells (HGEC) expressed mRNA of adenosine receptor subtype A1, A2a, and A2b but not A3. Stimulation of HGEC with adenosine or adenosine receptor agonists induced mRNA expression of iNOS and production of nitric oxide (NO) by HGEC. It was demonstrated that cAMP and phosphorylation of CREB were involved in the intracellular signal transduction via adenosine receptors on HGEC. Interestingly, it was also revealed that IL-15 induced NO production by HGEC, probably via ERK1/2 activation. Present results clearly suggest that the cellular functions in periodontal resident cells can be regulated by adenosine.
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