ADENOSINE A(3) RECEPTOR AGONISTS INHIBIT MURINE MACROPHAGE TUMOR-NECROSIS-FACTOR-ALPHA PRODUCTION IN-VITRO AND IN-VIVO

Adenosine and related analogs have been shown to regulate a variety of cell functions through different classes of adenosine receptors. Muri ne J774.1 macrophage cells were found to predominantly express adenosi ne A(3) receptor RNA relative to adenosine A(1) receptor or adenosine A(2) receptor RNA. Adenosine receptor agonists, in a dose-dependent ma nner characteristic of the adenosine A(3) receptor, blocked endotoxin- induction of the TNF-alpha gene and TNF-alpha protein expression in th e J774.1 macrophage cell line. The adenosine A(3) receptor antagonist BW-1433 dose-dependently reversed this adenosine receptor agonist inhi bitory effect on TNF-alpha gene expression. Thus, the binding of adeno sine receptor agonists to the adenosine A(3) receptor interrupts the e ndotoxin CD14 receptor signal transduction pathway and blocks inductio n of cytokine TNF-alpha, revealing a novel cross-talk between the muri ne adenosine Ag receptor and the endotoxin CD14 receptor in J774.1 mac rophages.