Modulation of NF-κB activation by resveratrol in LPS treated human intestinal cells results in downregulation of PGE2 production and COX-2 expression

Toxicol In Vitro. 2012 Oct;26(7):1122-8. doi: 10.1016/j.tiv.2012.06.015. Epub 2012 Jul 6.

Abstract

Resveratrol is a natural phytoalexin present in a variety of plant species, such as grapes and red wine, that is well known for its anti-inflammatory effects. In addition, a cancer chemotherapeutic activity of resveratrol has been described. Here we evaluated the effect of resveratrol on COX-2 and prostaglandin E(2) production in human intestinal cells Caco-2 cells treated with lipopolysaccharide (LPS). Resveratrol concentration-dependently inhibited the expression of COX-2 mRNA in the LPS-treated cells, as well as protein expression, resulting in a decreased production of PGE(2). In order to investigate the mechanisms through which resveratrol exhibited these anti-inflammatory effects, we examined the activation of IκB in LPS-stimulated intestinal cells. Results demonstrated that resveratrol inhibited the translocation of NF-κB p65 subunits from the cytosol to the nucleus, which correlated with its inhibitory effects on IκBα phosphorylation and degradation. These results suggest that the down-regulation of COX-2 and PGE(2) by resveratrol may be related to NF-κB inhibition through the negative regulation of IKK phosphorylation in intestinal cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antioxidants / pharmacology*
  • Caco-2 Cells
  • Cell Line
  • Cell Survival / drug effects
  • Cells, Cultured
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / metabolism*
  • Dinoprostone / genetics
  • Dinoprostone / metabolism*
  • Down-Regulation / drug effects
  • Enterocytes / drug effects*
  • Enterocytes / metabolism
  • Enterocytes / pathology
  • Gene Expression Regulation, Enzymologic / drug effects
  • Humans
  • Lipopolysaccharides / pharmacology
  • NF-kappa B / biosynthesis
  • NF-kappa B / drug effects*
  • Resveratrol
  • Stilbenes / pharmacology*

Substances

  • Antioxidants
  • Lipopolysaccharides
  • NF-kappa B
  • Stilbenes
  • Cyclooxygenase 2
  • PTGS2 protein, human
  • Dinoprostone
  • Resveratrol