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
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.