Activation of the Adenosine A3 Receptor in RAW 264.7 Cells Inhibits Lipopolysaccharide-Stimulated Tumor Necrosis Factor- Release by Reducing Calcium-Dependent Activation of Nuclear

Bacterial lipopolysaccharide (LPS) activates the immune sys-tem and promotes inflammation via Toll-like receptor (TLR) 4, which regulates the synthesis and release of tumor necrosis factor (TNF)- and other inflammatory cytokines. Previous studies have shown that the nucleoside adenosine suppresses LPS-stimulated TNF- release in human UB939 macrophages by activating an adenosine A3 receptor (A3AR) subtype on these cells. In this study, we examined the mechanism(s) un-derlying A3AR-dependent inhibition of TNF- release in a mouse (RAW 264.7) cell line. Treatment of RAW 264.7 cells with LPS (3 g/ml) increased TNF- release, which was reduced in a dose-dependent manner by adenosine analogs N6-(3-iodo-benzyl)-adenosine-5-N-methyluronamide (IB-MECA) and R-phenylisopropyladenosine and reversed by selective A3A