anti-inflammatory preconditioning by agonists of adenosine a1 receptor抗炎预处理腺苷a1受体受体激动剂.pdfVIP

Anti-Inflammatory Preconditioning by Agonists of Adenosine A1 Receptor 1 2 1 1 3 3 Sigal Nakav , Cidio Chaimovitz , Yuval Sufaro , Eli C. Lewis , Gad Shaked , David Czeiger , Moshe Zlotnik2, Amos Douvdevani1,2* 1 Department of Clinical Biochemistry, Soroka Medical University Center and Ben-Gurion University of the Negev, Beer-Sheva, Israel, 2 Department of Nephrology, Soroka Medical University Center and Ben-Gurion University of the Negev, Beer-Sheva, Israel, 3 Department of General Surgery, Soroka Medical University Center and Ben-Gurion University of the Negev, Beer-Sheva, Israel Abstract Background: Adenosine levels rise during inflammation and modulate inflammatory responses by engaging with four different G protein-coupled receptors. It is suggested that adenosine exhibits pro-inflammatory effects through its A1 receptor (A R), and anti-inflammatory effects through A receptor (A R). Therefore, understanding of the mechanisms that 1 2A 2A govern adenosine receptor regulation may advance treatment of various inflammatory disorders. We previously reported that peak A1R expression during leukocyte recruitment, is followed by a peak in A2AR during inflammation resolution. Principal Findings: Here, we examined whether A R activation sequentially induces A R expression and by this reverses 1 2A inflammation. The effect of adenosine on A1R mediated A2AR expression was examined in peritoneal macrophages (PMW) and primary peritoneal mesothelial cells (PMC) in vitro. Induction of A2AR was inhibited by pertus