Adenosine A3 receptor agonists inhibit macrophage tumor necrosis factor-? production

Adenosine and related analogs regulate a variety of cell functions through different classes of adenosine receptors. Murine J774.1 macrophage cells predominantly express adenosine A3 receptor RNA relative to adenosine A1 receptor or adenosine A2 receptor RNA. Adenosine receptor agonists, in a dose-dependent manner characteristic of the adenosine A3 receptor, blocked endotoxin-induction of the tumor necrosis factor-α (TNF-α) gene and TNF-α protein expression in the J774.1 macrophage cell line. The adenosine A3 receptor antagonist BW-1433 dose dependently reversed this adenosine receptor agonist inhibitory effect on TNF-α gene expression. Thus, the binding of adenosine receptor agonists to the adenosine A3 receptor interrupts the endotoxin CD14 receptor signal transduction pathway and blocks induction of cytokine TNF-α, thus revealing a novel cross talk between the murine adenosine A3 receptor and the endotoxin CD14 receptor in J774.1 macrophages. Drug Dev. Res. 39:388–392, 1996. © 1997 Wiley-Liss, Inc.