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Adenosine regulates the production of interleukin‐6 by human gingival fibroblasts via cyclic AMP/protein kinase A pathway
Author(s) -
Murakami Shinya,
Terakura Mami,
Kamatani Takeyuki,
Hashikawa Tomoko,
Saho Teruyuki,
Shimabukuro Yoshio,
Okada Hiroshi
Publication year - 2000
Publication title -
journal of periodontal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.31
H-Index - 83
eISSN - 1600-0765
pISSN - 0022-3484
DOI - 10.1034/j.1600-0765.2000.035002093.x
Subject(s) - adenosine , forskolin , adenosine kinase , adenosine receptor , endocrinology , medicine , protein kinase a , adenosine a3 receptor , adenosine a1 receptor , chemistry , receptor , microbiology and biotechnology , kinase , biology , adenosine deaminase , agonist
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 by HGF. Ligation of adenosine receptors with adenosine or its related analogue, 2‐chloroadenosine (2‐CADO), increased IL‐6 production by HGF without any 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. Interestingly, these cAMP‐arising reagents and the permeable cAMP analogue, dibutyryl cAMP (dbtcAMP), also increased IL‐6 production by HGF. These results suggest that cAMP is involved in adenosine‐ induced IL‐6 production by HGF. 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. These results provide new evidence for the possible effects of adenosine or its related analogue as an immunomodulator in inflammatory periodontal lesions.