Aspirin inhibits tumor necrosis factor-alpha gene expression in murine tissue macrophages

Aspirin has been reported to inhibit the activation of nuclear factor-kappa B (NF-kappa B) through stabilization of inhibitor kappa B (I kappa B). This observation led us to investigate the role of aspirin in suppressing the activation of the NF-kappa B-regulated tumor necrosis factor-alpha (TNF-alpha) gene expression in primary macrophages. We now report that therapeutic doses of aspirin suppress lipopolysaccharide-inducible NF-kappa B binding to an NF-kappa B binding site in the TNF-alpha promoter, lipopolysaccharide-induced TNF-alpha mRNA accumulation, and protein secretion. I kappa B is also stabilized under these conditions. The aspirin-initiated stabilization of I kappa B, suppression of induced TNF-alpha mRNA, and NF-kappa B binding to the TNF-alpha promoter are blocked by pretreatment with pertussis toxin. These studies suggest that aspirin may exert significant anti-inflammatory effects by suppressing the production of macrophage-derived inflammatory mediators.