Abstract

Aspirin has been reported to inhibit the activation of nuclear factor-κB (NF-κB) through stabilization of inhibitor κB (IκB). This observation led us to investigate the role of aspirin in suppressing the activation of the NF-κB-regulated tumor necrosis factor-α (TNF-α) gene expression in primary macrophages. We now report that therapeutic doses of aspirin suppress lipopolysaccharide-inducible NF-κB binding to an NF-κB binding site in the TNF-α promoter, lipopolysaccharide-induced TNF-α mRNA accumulation, and protein secretion. IκB is also stabilized under these conditions. The aspirin-initiated stabilization of IκB, suppression of induced TNF-α mRNA, and NF-κB binding to the TNF-α 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.