Induction of IκBα Expression as a Mechanism Contributing to the Anti-inflammatory Activities of Peroxisome Proliferator-activated Receptor-α Activators

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作者：

P Delerive，P Gervois，JC Fruchart，B Staels

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摘要：

Chronic inflammation is a hallmark of degenerative diseases such as atherosclerosis. Peroxisome proliferator-activated receptors (PPARs) are transcription factors belonging to the nuclear receptor superfamily, which are expressed in the cells of the atherosclerosic lesion. PPARα ligands have been reported to exert anti-inflammatory activities in different cell types by antagonizing the transcriptional activity of NF-κB. In the present study, the influence of PPARα activators on the NF-κB signaling pathway was investigated. Our results show that fibrates, synthetic PPARα activators, induced the expression of the inhibitory protein IκBα in human aortic smooth muscle cells as well as in primary human hepatocytes, whereas neither IκB-kinase activity nor the degradation rate of IκBα were affected. Using PPARα-null mice, we demonstrated that fibrates induced IκBα in liver in vivo and that this action required PPARα. Furthermore, fibrate treatment induced IκBα protein expression in the cytoplasm and also enhanced IL-1β-induced accumulation of IκBα protein in the nucleus. These actions of fibrates on IκBα expression were accompanied by a decrease in NF-κB DNA binding activity as demonstrated by electrophoretic mobility shift assays. Taken together, these data provide an additional molecular mechanism for the anti-inflammatory activity of PPARα agonists and reinforce their potential use in the treatment of inflammatory diseases.

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关键词：

DNA analysis paraffin-embedded sample flow cytometry laser scanning cytometry

DOI：

10.1074/jbc.M004045200

被引量：

1497

年份：

2000