Expression of cyclooxygenase-2 in rat vascular smooth muscle cells is unrelated to nuclear factor-kappaB activation

Life Sci. 1999;64(14):1231-42. doi: 10.1016/s0024-3205(99)00055-7.


The promoter region of cyclooxygenase-2 (COX-2) gene contains binding sites for a number of important transcription factors including cyclic AMP response element, nuclear factor-IL6, nuclear factor-kappaB (NF-kappaB) and TGF-beta response element. Several reports have documented that the activation of NF-kappaB triggers the expression of COX-2 gene. In the present study, NF-kappaB was activated by TNF-alpha in rat aortic smooth muscle cells as demonstrated by electrophoretic mobility shift assay. The activity of NF-kappaB induced by TNF-alpha was blocked by calpain inhibitor I, a potent NF-kappaB inhibitor. However, the activation of NF-kappaB was not related to the expression of COX-2 induced by TNF-alpha since calpain inhibitor I blocked the activation of NF-kappaB but not the expression of COX-2 mRNA or protein. Mutation of rat COX-2 NF-kappaB-like sites in the promoter region did not significantly reduce the promoter activity. These results suggest that the transcriptional regulation of COX-2 expression by NF-kappaB depends upon the types of cells studied and that activation of this transcription factor alone does not play an important role in the expression of COX-2 in rat smooth muscle cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calpain / antagonists & inhibitors
  • Cyclooxygenase 2
  • Gene Expression Regulation, Enzymologic*
  • Isoenzymes / genetics*
  • Muscle, Smooth, Vascular / enzymology*
  • NF-kappa B / physiology*
  • Promoter Regions, Genetic
  • Prostaglandin-Endoperoxide Synthases / genetics*
  • Rats
  • Tumor Necrosis Factor-alpha / pharmacology


  • Isoenzymes
  • NF-kappa B
  • Tumor Necrosis Factor-alpha
  • Cyclooxygenase 2
  • Prostaglandin-Endoperoxide Synthases
  • Calpain