PPARalpha blocks glucocorticoid receptor alpha-mediated transactivation but cooperates with the activated glucocorticoid receptor alpha for transrepression on NF-kappaB.

ABSTRACT: Glucocorticoid receptor alpha (GRalpha) and peroxisome proliferator-activated receptor alpha (PPARalpha) are transcription factors with clinically important immune-modulating properties. Either receptor can inhibit cytokine gene expression, mainly through interference with nuclear factor kappaB (NF-kappaB)-driven gene expression. The present work aimed to investigate a functional cross-talk between PPARalpha- and GRalpha-mediated signaling pathways. Simultaneous activation of PPARalpha and GRalpha dose-dependently enhances transrepression of NF-kappaB-driven gene expression and additively represses cytokine production. In sharp contrast and quite unexpectedly, PPARalpha agonists inhibit the expression of classical glucocorticoid response element (GRE)-driven genes in a PPARalpha-dependent

SUBMITTER: Bougarne N 

PROVIDER: S-EPMC2678648 | biostudies-literature | 2009 May

REPOSITORIES: biostudies-literature