PT  - JOURNAL ARTICLE
AU  - Rodney E. Shackelford
AU  - Paul B. Alford
AU  - Yan Xue
AU  - Sheau-Fung Thai
AU  - Dolph O. Adams
AU  - Salvatore Pizzo
TI  - Aspirin Inhibits Tumor Necrosis Factor<strong>-</strong>α Gene Expression in Murine Tissue Macrophages
AID  - 10.1124/mol.52.3.421
DP  - 1997 Sep 01
TA  - Molecular Pharmacology
PG  - 421--429
VI  - 52
IP  - 3
4099  - http://molpharm.aspetjournals.org/content/52/3/421.short
4100  - http://molpharm.aspetjournals.org/content/52/3/421.full
SO  - Mol Pharmacol1997 Sep 01; 52
AB  - 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.