Functions and regulatory mechanisms of adenosin in inflammatory periodontal tissues

有证据表明，腺苷，一种内源性核苷，可以调节参与炎症反应的细胞的各种功能。在这项研究中，我们研究了腺苷对牙周组织驻留细胞的各种功能的影响。我们证明，人牙龈成纤维细胞（HGF）表达腺苷受体亚型A1，A2 a和A2 b的mRNA，但不A3。用腺苷或腺苷受体激动剂刺激HGF诱导IL-6和IL-8产生。cAMP、PKA、PKC和PLC通过HGF上的腺苷受体参与细胞内信号转导。此外，腺苷刺激还上调HGF中透明质酸合成酶的mRNA表达。另一方面，腺苷刺激下调了IL-1β诱导的ICAM-1在HGF上的表达，从而抑制了LFA-1依赖的淋巴细胞与HGF的粘附。我们还表明，人牙龈上皮细胞（HGEC）表达腺苷受体亚型A1，A2 a和A2 b的mRNA，但不A3。用腺苷或腺苷受体激动剂刺激HGEC诱导iNOS mRNA表达和HGEC产生一氧化氮（NO）。结果表明，cAMP和CREB的磷酸化通过腺苷受体参与细胞内信号转导。有趣的是，还揭示了IL-15诱导HGEC产生NO，可能是通过ERK 1/2激活。目前的结果清楚地表明，在牙周驻留细胞的细胞功能可以调节腺苷。

Several lines of evidence have demonstrated that adenosine, an endogenous nucleoside, can modulate the various functions of cells involved in inflammatory responses. In this study, we investigated the effects of adenosine on various functions of resident cells in periodontal tissues. We demonstrated that human gingival fibroblasts (HGF) expressed mRNA of adenosine receptor subtype A1, A2a, and A2b but not A3. Stimulation of HGF with adenosine or adenosine receptor agonists induced IL-6 and IL-8 production. It was also revealed that CAMP, PKA, PKC and PLC were involved in the intracellular signal transduction via adenosine receptors on HGF. In addition, the adenosine stimulation also upregulated mRNA expression of hyaluronan synthase in HGF. On the other hand, adenosine stimulation downregulated the IL-1β-induced ICAM-1 egression on HGF, that resulted in the inhibition of LFA-1-dependent lymphocyte adhesion to HGF. We also demonstrated that human gingival epithelial cells (HGEC) expressed mRNA of adenosine receptor subtype A1, A2a, and A2b but not A3. Stimulation of HGEC with adenosine or adenosine receptor agonists induced mRNA expression of iNOS and production of nitric oxide (NO) by HGEC. It was demonstrated that cAMP and phosphorylation of CREB were involved in the intracellular signal transduction via adenosine receptors on HGEC. Interestingly, it was also revealed that IL-15 induced NO production by HGEC, probably via ERK1/2 activation. Present results clearly suggest that the cellular functions in periodontal resident cells can be regulated by adenosine.