Stimulation of Adenosine A2A Receptor Regulates Peroxisome Proliferator Activated Receptors in Macrophages

Abstract

Adenosine signals via A2A receptor to inhibit many immune/inflammatory reactions. The mechanisms involved are not completely clear. Peroxisome proliferators-activated receptors (PPARs) are transcription factors that regulate lipid and glucose homeostasis and also are able to regulate the expression of inflammatory molecules in macrophages. In this study, we assessed whether adenosine and a selective A2A receptor agonists (ATL313) regulate the expression or/and activation of PPARs in macrophages. Adenosine and ATL313 increased expression of PPAR alpha, PPAR gamma and PPAR beta in THP-1 cells and mouse peritoneal macrophages. In mouse peritoneal macrophages adenosine as well as ATL313 were able to suppress LPS-induced PPAR gamma downregulation. EMSA showed that the binding of PPARs to their peroxisome proliferator response element (PPRE) was enhanced by adenosine. Thus, A2A receptor activation increase the expression and activation of PPARs and this may be an important mechanism by which adenosine inhibits inflammation. This work was supported by NIH HL078679, HL080569 and AHA 0430151N to Y. Huo.