Peroxisome proliferator activated receptor gamma agonists suppress TNFalpha-induced ICAM-1 expression by endothelial cells in a manner potentially dependent on inhibition of reactive oxygen species

Immunol Lett. 2008 Apr 15;117(1):63-9. doi: 10.1016/j.imlet.2007.12.002. Epub 2007 Dec 31.

Abstract

In this study, we investigated the anti-inflammatory effect of various peroxisome proliferator activated receptor gamma (PPARgamma) agonists (15-deoxy-Delta12,14-prostaglandin J(2), troglitazone, rosiglitazone, ciglitazone) on human aortic endothelial cells. Pretreatment with PPARgamma agonists abrogated tumor necrosis factor alpha (TNFalpha)-induced expression of intercellular adhesion molecule-1 (ICAM-1) and subsequent monocytic adhesion by endothelial cells. Because reactive oxygen species (ROS) have been reported to play important roles in pro-inflammatory signal transduction, the involvement of ROS was investigated as a potential mechanism of anti-inflammatory effect of PPARgamma ligands. Consistent with previous reports in other cell types, blockade of TNFalpha-induced ROS by treatment with N-acetylcysteine, diphenylene iodonium or NADPH oxidase 4 (NOX4) siRNA suppressed TNFalpha-induced ICAM-1 expression and subsequent monocytic adhesion, indicating that TNFalpha mediates pro-inflammatory signals via NOX4-dependent ROS generation in human endothelial cells. Finally, pretreatment with PPARgamma agonists significantly suppressed TNFalpha-induced increases of intracellular ROS. Our results collectively suggest that PPARgamma agonists might exert an anti-inflammatory effect on endothelial cells in a ROS-dependent manner.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Inflammatory Agents / pharmacology*
  • Cells, Cultured
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / drug effects*
  • Endothelium, Vascular / metabolism
  • Humans
  • Intercellular Adhesion Molecule-1 / metabolism*
  • NADPH Oxidase 4
  • NADPH Oxidases / metabolism
  • PPAR gamma / agonists*
  • Reactive Oxygen Species / antagonists & inhibitors
  • Reactive Oxygen Species / metabolism*
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors*
  • U937 Cells

Substances

  • Anti-Inflammatory Agents
  • PPAR gamma
  • Reactive Oxygen Species
  • Tumor Necrosis Factor-alpha
  • Intercellular Adhesion Molecule-1
  • NADPH Oxidase 4
  • NADPH Oxidases
  • NOX4 protein, human