标题：PPARα blocks glucocorticoid receptor α-mediated transactivation but cooperates with the activated glucocorticoid receptor α for transrepression on NF-κB
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2009
卷号：106
期号：18
页码：7397-7402
DOI：10.1073/pnas.0806742106
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Glucocorticoid receptor {alpha} (GR{alpha}) and peroxisome proliferator-activated receptor {alpha} (PPAR{alpha}) are transcription factors with clinically important immune-modulating properties. Either receptor can inhibit cytokine gene expression, mainly through interference with nuclear factor {kappa}B (NF-{kappa}B)-driven gene expression. The present work aimed to investigate a functional cross-talk between PPAR{alpha}- and GR{alpha}-mediated signaling pathways. Simultaneous activation of PPAR{alpha} and GR{alpha} dose-dependently enhances transrepression of NF-{kappa}B-driven gene expression and additively represses cytokine production. In sharp contrast and quite unexpectedly, PPAR{alpha} agonists inhibit the expression of classical glucocorticoid response element (GRE)-driven genes in a PPAR{alpha}-dependent manner, as demonstrated by experiments using PPAR{alpha} wild-type and knockout mice. The underlying mechanism for this transcriptional antagonism relies on a PPAR{alpha}-mediated interference with the recruitment of GR{alpha
关键词：cross-talk ; gluconeogenesis ; inflammation ; hyperinsulinema ; side effects
