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

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• 作者：Yuyeon Jung ; Seungjeong Song ; Chulhee Choi
• 关键词：Peroxisome proliferator activated receptor γ ; Tumor necrosis factor ; //www.sciencedirect.com/scidirimg/entities/204e.gif"" alt=""greek small letter alpha"" title=""greek small letter alpha"" border=""0""> ; Intercellular adhesion molecule-1 ; R
• 刊名：Immunology Letters
• 出版年：2008
• 出版时间：15 April 2008
• 年：2008
• 卷：117
• 期：1
• 页码：63-69
• 全文大小：557 K

文摘

In this study, we investigated the anti-inflammatory effect of various peroxisome proliferator activated receptor gamma (PPARγ) agonists (15-deoxy-Δ12,14-prostaglandin J₂, troglitazone, rosiglitazone, ciglitazone) on human aortic endothelial cells. Pretreatment with PPARγ agonists abrogated tumor necrosis factor (TNF)-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 PPARγ ligands. Consistent with previous reports in other cell types, blockade of TNF-induced ROS by treatment with N-acetylcysteine, diphenylene iodonium or NADPH oxidase 4 (NOX4) siRNA suppressed TNF-induced ICAM-1 expression and subsequent monocytic adhesion, indicating that TNF mediates pro-inflammatory signals via NOX4-dependent ROS generation in human endothelial cells. Finally, pretreatment with PPARγ agonists significantly suppressed TNF-induced increases of intracellular ROS. Our results collectively suggest that PPARγ agonists might exert an anti-inflammatory effect on endothelial cells in a ROS-dependent manner.