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Study of the effects of adenosine on the cell function in cells comprising human periodontal tissue cells

腺苷对人牙周组织细胞细胞功能影响的研究

基本信息

批准号：
10671965
负责人：
SHIMABUKURO Yoshio
金额：
$ 2.05万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

项目摘要

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.

据报道，腺苷可改变参与炎症反应的细胞的多种功能。然而，腺苷对人牙龈成纤维细胞（HGF），炎症牙周病变中的免疫调节细胞之一的影响，仍有待建立。在这项研究中，我们研究了腺苷对HGF产生白细胞介素（IL）-6，8和诱导透明质酸合成酶（HAS）mRNA的影响。腺苷受体与腺苷或其相关类似物2-氯腺苷（2CADO）的连接增加了HGF在没有任何其他刺激的情况下产生的IL-6，8。此外，腺苷和2CADO提高环磷酸腺苷（cAMP）在肝细胞生长因子的水平，前列腺素E1和毛喉素。有趣的是，这些产生cAMP的试剂和可渗透的cAMP类似物，二丁酰cAMP（dbtcAMP），也增加了HGF的IL-6 - 8的产生。这些结果表明，cAMP参与了腺核苷诱导的HGF产生IL-6。有趣的是，腺苷诱导的IL-6产生被蛋白激酶A（PKA）抑制剂H89抑制，表明cAMP/PKA通路参与了诱导。此外，使用腺苷受体亚型特异性拮抗剂的实验表明，腺苷诱导的HGF产生IL-6至少部分是由腺苷A2 b受体介导的。2CADO还可增强HGF中HASmRNA的表达。这些结果为腺苷或其相关类似物作为免疫调节剂在炎症性牙周病变中的可能作用提供了新的证据。