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

Publication ,  Journal Article
Shackelford, RE; Alford, PB; Xue, Y; Thai, SF; Adams, DO; Pizzo, S
Published in: Mol Pharmacol
September 1997

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.

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Published In

Mol Pharmacol

DOI

ISSN

0026-895X

Publication Date

September 1997

Volume

52

Issue

3

Start / End Page

421 / 429

Location

United States

Related Subject Headings

  • Virulence Factors, Bordetella
  • Tumor Necrosis Factor-alpha
  • Transcription Factors
  • Transcription Factor RelB
  • RNA, Messenger
  • Proto-Oncogene Proteins
  • Promoter Regions, Genetic
  • Pharmacology & Pharmacy
  • Pertussis Toxin
  • NF-kappa B
 

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Shackelford, R. E., Alford, P. B., Xue, Y., Thai, S. F., Adams, D. O., & Pizzo, S. (1997). Aspirin inhibits tumor necrosis factoralpha gene expression in murine tissue macrophages. Mol Pharmacol, 52(3), 421–429. https://doi.org/10.1124/mol.52.3.421
Shackelford, R. E., P. B. Alford, Y. Xue, S. F. Thai, D. O. Adams, and S. Pizzo. “Aspirin inhibits tumor necrosis factoralpha gene expression in murine tissue macrophages.Mol Pharmacol 52, no. 3 (September 1997): 421–29. https://doi.org/10.1124/mol.52.3.421.
Shackelford RE, Alford PB, Xue Y, Thai SF, Adams DO, Pizzo S. Aspirin inhibits tumor necrosis factoralpha gene expression in murine tissue macrophages. Mol Pharmacol. 1997 Sep;52(3):421–9.
Shackelford, R. E., et al. “Aspirin inhibits tumor necrosis factoralpha gene expression in murine tissue macrophages.Mol Pharmacol, vol. 52, no. 3, Sept. 1997, pp. 421–29. Pubmed, doi:10.1124/mol.52.3.421.
Shackelford RE, Alford PB, Xue Y, Thai SF, Adams DO, Pizzo S. Aspirin inhibits tumor necrosis factoralpha gene expression in murine tissue macrophages. Mol Pharmacol. 1997 Sep;52(3):421–429.

Published In

Mol Pharmacol

DOI

ISSN

0026-895X

Publication Date

September 1997

Volume

52

Issue

3

Start / End Page

421 / 429

Location

United States

Related Subject Headings

  • Virulence Factors, Bordetella
  • Tumor Necrosis Factor-alpha
  • Transcription Factors
  • Transcription Factor RelB
  • RNA, Messenger
  • Proto-Oncogene Proteins
  • Promoter Regions, Genetic
  • Pharmacology & Pharmacy
  • Pertussis Toxin
  • NF-kappa B