Adenosine regulates the production of interleukin-6 by human gingival fibroblasts via cyclic AMP/protein kinase A pathway

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 in flamed periodontal lesions, remains to be established. In this study, we ex amined the influence of adenosine on the production of interleukin (IL)-6 b y HGF. Ligation of adenosine receptors with adenosine or its related analog ue, 2-chloroadenosine (2-CADO), increased IL-6 production by HGF without an y other stimuli. In addition, adenosine and 2-CADO enhanced the cyclic AMP (cAMP) level in HGF as did prostaglandin E-1 (PGE(1)) and forskolin. Intere stingly, these cAMP-arising reagents and the permeable cAMP analogue, dibut yryl cAMP (dbtcAMP),also increased IL-6 production by HGF. These results su ggest that cAMP is involved in adenosine-induced IL-6 production by HGF. Ad enosine-induced IL-6 production was suppressed by protein kinase A (PKA) in hibitor, H89, indicating that cAMP/PKA pathway is involved in the induction . Moreover, the experiments using antagonists specific for adenosine recept or subtypes revealed that the adenosine-induced IL-6 production by HGF was, at least in part, mediated by the adenosine A2b receptor. These results pr ovide new evidence for the possible effects of adenosine or its related ana logue as an immunomodulator in inflammatory periodontal lesions.