Aspirin inhibits tumor necrosis factoralpha gene expression in murine tissue macrophages.

Published

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

Pubmed Central ID

  • 9281604

Electronic International Standard Serial Number (EISSN)

  • 1521-0111

International Standard Serial Number (ISSN)

  • 0026-895X

Digital Object Identifier (DOI)

  • 10.1124/mol.52.3.421

Language

  • eng