Aspirin inhibits tumor necrosis factoralpha gene expression in murine tissue macrophages.
Journal Article (Journal Article)
Aspirin has been reported to inhibit the activation of nuclear factor-kappaB (NF-kappaB) through stabilization of inhibitor kappaB (IkappaB). This observation led us to investigate the role of aspirin in suppressing the activation of the NF-kappaB-regulated tumor necrosis factor-alpha (TNF-alpha) gene expression in primary macrophages. We now report that therapeutic doses of aspirin suppress lipopolysaccharide-inducible NF-kappaB binding to an NF-kappaB binding site in the TNF-alpha promoter, lipopolysaccharide-induced TNF-alpha mRNA accumulation, and protein secretion. IkappaB is also stabilized under these conditions. The aspirin-initiated stabilization of IkappaB, suppression of induced TNF-alpha mRNA, and NF-kappaB 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.
Full Text
Duke Authors
Cited Authors
- Shackelford, RE; Alford, PB; Xue, Y; Thai, SF; Adams, DO; Pizzo, S
Published Date
- September 1997
Published In
Volume / Issue
- 52 / 3
Start / End Page
- 421 - 429
PubMed ID
- 9281604
International Standard Serial Number (ISSN)
- 0026-895X
Digital Object Identifier (DOI)
- 10.1124/mol.52.3.421
Language
- eng
Conference Location
- United States