Abstract

Adenosine, an endogenous nucleoside, has a plethora of biological actions on a large variety of cells and can modulate the various functions of cells involved in inflammatory responses. On the other hand, production of extracellular matrices is one of the critical functions of fibroblasts. Among various extracellular matrices, hyaluronate (HA) plays important roles in migration, growth and differentiation of a variety of cells during the course of inflammatory reactions and process of wound healing.In this study, we investigated the expression of adenosine receptor subtypes in human gingival fibroblasts (HGF) and examined the effects of adenosine on the HA production of HGF by utilizing various agonists specific for adenosine receptor subtypes.Concerning the expression of adenosine receptors, RT-PCR analysis revealed that HGF expressed adenosine receptor A1, A2 a, and A2 b, but not A3 mRNA. Ligation of adenosine receptors by adenosine or adenosine analogue, 2-chlor-oadenosine (2 CADO) and N6-cyclopentyladenosine (CPA; A1 adenosine receptor agonist) but not CGS-21680 (A2 a adenosine receptor agonist) induced the expression of HA synthase mRNA, which is responsible for HA production in HGF. These results suggest that intracellular signal (s) via A1 adenosine receptor may play a central role for the upregulation of HA production by activated HGF in inflamed periodontal lesions.These results provide new evidence for the possible involvement of adenosine in the regulation of extracellular matrix production during the course of inflammatory responses in periodontal tissues.

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