Activation of PPARγ inhibits pro-inflammatory cytokines production by upregulation of miR-124 in vitro and in vivo

Abstract

Peroxisome proliferator-activated receptor gamma (PPARγ) and miR-124 have been reported to play important roles in regulation of inflammation. However, the underlying anti-inflammatory mechanisms remain not well understood. In the present study, we demonstrated that the expression level of PPARγ is positively correlated with that of miR-124 in patients with sepsis. Activation of PPARγ upregulates miR-124 and in turn inhibits miR-124 target gene. PPARγ bound directly to PPRE in the miR-124 promoter region, and enhanced the promoter transcriptional activity. PPARγ-induced miR-124 is involved in the suppression of pro-inflammatory cytokine in vitro and in vivo. These results suggest that PPARγ-induced miR-124 inhibits the production of pro-inflammatory cytokines is a novel PPARγ anti-inflammatory mechanism and also indicate that miR-124 may be a potential therapeutic target for the treatment of inflammatory diseases.