ACTIVATION OF ADENOSINE A(3) RECEPTORS ON MACROPHAGES INHIBITS TUMOR-NECROSIS-FACTOR-ALPHA

Citation
Cd. Mcwhinney et al., ACTIVATION OF ADENOSINE A(3) RECEPTORS ON MACROPHAGES INHIBITS TUMOR-NECROSIS-FACTOR-ALPHA, European journal of pharmacology, 310(2-3), 1996, pp. 209-216
Citations number
51
Categorie Soggetti
Pharmacology & Pharmacy
ISSN journal
00142999
Volume
310
Issue
2-3
Year of publication
1996
Pages
209 - 216
Database
ISI
SICI code
0014-2999(1996)310:2-3<209:AOAARO>2.0.ZU;2-6
Abstract
Murine macrophage-derived tumor necrosis factor alpha (TNF-alpha) gene expression has been shown to be dramatically induced by bacterial lip opolysaccharide, and to be dependent upon nuclear factor-kappa B (NF-k appa B) binding sites in its promoter for the lipopolysaccharide induc tion. Murine J774.1 macrophage cells were found to predominately expre ss the adenosine A(3) receptor RNA relative to adenosine A(1) receptor or adenosine A(2) receptor RNA. Adenosine receptor agonists, in a dos e-dependent manner characteristic of the adenosine A(3) receptor, bloc ked the endotoxin induction of the TNF-alpha gene and TNF-alpha protei n expression in the J774.1 macrophage cell line. The adenosine A(3) re ceptor antagonist BW-1433 dose-dependently reversed this adenosine inh ibitory effect on TNF-alpha gene expression. Thus, the binding of aden osine receptor agonists to the adenosine A(3) receptor interrupts the endotoxin CD14 receptor signal transduction pathway and blocks inducti on of cytokine TNF-alpha, revealing a novel cross-talk between the mur ine adenosine A(3) receptor and the endotoxin CD14 receptor in J774.1 macrophages.