GR-mediated Regulation of Cytokine Genes by MPA [Signal Transduction]

This study shows that P4 and MPA significantly increase the expression of the IL-12p40 and IL-12p35 genes, whereas IL-10 gene expression is suppressed in a dose-dependent manner. Moreover, these effects were abrogated when reducing the glucocorticoid receptor (GR) levels with siRNA. Using a combination of chromatin immunoprecipitation (ChIP), siRNA, and re-ChIP assays, we show that recruitment of the P4- and MPA-bound GR to the IL-12p40 promoter requires CCAAT enhancer-binding protein (C/EBP)-β and nuclear factor κB (NFκB), although recruitment to the IL-10 promoter requires signal transducer and activator of transcription (STAT)-3. These results suggest that both P4 and MPA may modulate inflammation in the ectocervix via this genomic mechanism.
Source: Journal of Biological Chemistry - Category: Chemistry Authors: Tags: Gene Regulation Source Type: research