Effects of adenosine on adhesion molecule expression and cytokine production in human PBMC depend on the receptor subtype activated

Publisher Website
Google Scholar
Abstract
Background and purpose: Adenosine suppresses immune responses through adenosine2A(A2A) receptors, by raising intracellular cAMP. Interleukin (IL)‐18 up‐regulates the expression of intercellular adhesion molecule (ICAM)‐1 on monocytes, leading to production of pro‐inflammatory cytokines such as IL‐12, interferon (IFN)‐γand tumor necrosis factor (TNF)‐αby human peripheral blood mononuclear cells (PBMC). We have previously demonstrated that elevation of cAMP inhibits this IL‐18‐induced expression of adhesion molecules. In the present study, we examined the effect of adenosine on the IL‐18‐induced up‐regulation of ICAM‐1 on human monocytes and production of IL‐12, IFN‐γand TNF‐αby PBMC.Experimental approach: The expression of ICAM‐1 was examined by flow cytometry. IL‐12, IFN‐γand TNF‐αwere determined by ELISA assay.Key results: Adenosine inhibited the IL‐18‐induced up‐regulation of ICAM‐1 on human monocytes and it abolished the IL‐18‐enhanced production of IL‐12, IFN‐γand TNF‐α. While an A2Areceptor antagonist reversed the action of adenosine, an A1or A3receptor antagonist enhanced them. An A2Areceptor agonist, CGS21680, mimicked the effects of adenosine and its effects were abolished not only by the A2Areceptor antagonist but also by A1or A3receptor agonists. Activation via A2Areceptors resulted in elevation of cAMP in monocytes, whereas the stimulation of A1or A3receptors inhibited it, suggesting that intracellular signal transduction following ligation of A2Areceptors might be blocked by activation of A1or A3receptors.Conclusions and Implications: Adenosine differentially regulates IL‐18‐induced adhesion molecule expression and cytokine production through several subtypes of its receptors.British Journal of Pharmacology(2007)150, 816–822. doi:10.1038/sj.bjp.0707126