TY - JOUR
T1 - Activation of adenosine A3 receptors on macrophages inhibits tumor necrosis factor-
AU - McWhinney, Charlene D.
AU - Dudley, Mark W.
AU - Bowlin, Terry L.
AU - Peet, Norton P.
AU - Schook, Larry
AU - Bradshaw, Marita
AU - De, Mamata
AU - Borcherding, David R.
AU - Edwards, Carl K.
N1 - Funding Information:
The RBL-2H3-(ml) rat mast cell line was the generous gift of Dr. Michael Beaven, National Institutes of Health (NIH).
PY - 1996/8/29
Y1 - 1996/8/29
N2 - Murine macrophage-derived tumor necrosis factor alpha (TNF-α) gene expression has been shown to be dramatically induced by bacterial lipopolysaccharide, and to be dependent upon nuclear factor-κB (NF-κB) binding sites in its promoter for the lipopolysaccharide induction. Murine J774.1 macrophage cells were found to predominately express the 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 the endotoxin induction of the 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 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, revealing a novel cross-talk between the murine adenosine A3 receptor and the endotoxin CD14 receptor in J774.1 macrophages.
AB - Murine macrophage-derived tumor necrosis factor alpha (TNF-α) gene expression has been shown to be dramatically induced by bacterial lipopolysaccharide, and to be dependent upon nuclear factor-κB (NF-κB) binding sites in its promoter for the lipopolysaccharide induction. Murine J774.1 macrophage cells were found to predominately express the 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 the endotoxin induction of the 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 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, revealing a novel cross-talk between the murine adenosine A3 receptor and the endotoxin CD14 receptor in J774.1 macrophages.
KW - Adenosine A receptor
KW - Cross-talk
KW - Macrophage
KW - Receptor
KW - TNF-α (tumor necrosis factor α) inhibition
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U2 - 10.1016/0014-2999(96)00272-5
DO - 10.1016/0014-2999(96)00272-5
M3 - Article
C2 - 8884219
AN - SCOPUS:0030605935
VL - 310
SP - 209
EP - 216
JO - European Journal of Pharmacology
JF - European Journal of Pharmacology
SN - 0014-2999
IS - 2-3
ER -