Adenosine A3 receptor agonists inhibit murine macrophage tumor necrosis factor-alpha production in vitro and in vivo
Bowlin, T.L.; Borcherding, D.R.; Edwards, C.K.; McWhinney, C.D.
Cellular and Molecular Biology 43(3): 345-349
1997
ISSN/ISBN: 0145-5680 PMID: 9193789 Document Number: 483420
Adenosine and related analogs have been shown to regulate a variety of cell functions through different classes of adenosine receptors. Murine J774.1 macrophage cells were found to predominantly express adenosine A-3 receptor RNA relative to adenosine A-1 receptor or adenosine A-2 receptor RNA. Adenosine receptor agonists, in a dose-dependent manner characteristic of the adenosine A-3 receptor, blocked endotoxin-induction of the TNF-alpha gene and TNF-alpha protein expression in the J774.1 macrophage cell line. The adenosine A-3 receptor antagonist BW-1433 dose-dependently reversed this adenosine receptor agonist inhibitory effect on TNF-alpha gene expression. Thus, the binding of adenosine receptor agonists to the adenosine A-3 receptor interrupts the endotoxin CD14 receptor signal transduction pathway and blocks induction of cytokine TNF-alpha, revealing a novel cross-talk between the murine adenosine A-3 receptor and the endotoxin CD14 receptor in J774.1 macrophages.