| Co-Investigator(Kenkyū-buntansha) |
SAHO Teruyuki Osaka Univ. Fac. of Dentistry Instructor, 歯学部・附属病院, 助手 (10263295)
MURAKAMI Shinya Osaka Univ. Fac. of Dentistry Asst. Prof., 歯学部・附属病院, 講師 (70239490)
OKADA Hiroshi Osaka Univ. Fac. of Dentistry Prof. and Chair, 歯学部, 教授 (40038865)
IKEZAWA Kazuhiko Osaka Univ. Fac. of Dentistry Instructor, 歯学部, 助手 (80294114)
平野 裕之 大阪大学, 歯学部, 助手 (40260640)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1999: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1998: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Research Abstract |
Adenosine has been reported to alter a variety functions of the cells that participate in inflammatory responses. However, the effect (s) of adenosine on human gingival fibroblasts (HGF), one of the immunomodulator cells in inflamed periodontal lesions, remains to be established. In this study, we examined the influence of adenosine on the production of interleukin (IL)-6, 8 and induction of hyaluronan synthase (HAS) mRNA by HGF. Ligation of adenosine receptors with adenosine or its related analogue, 2-chloroadenosine (2CADO), increased IL-6, 8 production by HGF without any other stimuli. In addition, adenosine and 2CADO enhanced the cyclic AMP (cAMP) level in HGF as prostaglandin E1 and forskolin did. Interestingly, these cAMP-arising reagents and the permeable cAMP analogue, dibutyryl cAMP (dbtcAMP), also increased IL-6 8 production by HGF. These results suggest that cAMP is involved in adenosine-induced IL-6 production by HGF. Interestingly, adenosine-induced IL-6 production was suppressed by protein kinase A (PKA) inhibitor, H89, indicating that cAMP/PKA pathway is involved in the induction. Moreover, the experiments using antagonists specific for adenosine receptor subtypes revealed that the adenosine-induced IL-6 production by HGF was, at least in part, mediated by the adenosine A2b receptor. Also 2CADO enhanced HASmRNA in HGF. These results provide new evidence for the possible effects of adenosine or its related analogue as an immunomodulator in inflammatory periodontal lesions.
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