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.
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.
Jung
Yuyeon
Y
Department of Life and Pharmaceutical Sciences, Ewha University, Seoul 120-750, Republic of Korea.
Song
Seungjeong
S
Choi
Chulhee
C
D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000378:metabolism; D047495:PPAR gamma / Q000819:agonists*; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D020298:U937 Cells
D000893:Anti-Inflammatory Agents; D047495:PPAR gamma; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C498910:NOX4 protein, human