Transcriptional Modulation of the Immune Response by Peroxisome Proliferator-Activated Receptor-α Agonists in Autoimmune Disease

摘要: Peroxisome proliferator-activated receptor-alpha (PPARalpha) agonists have been shown to a therapeutic benefit in experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis (MS). In this study, we investigated the mechanism by which PPARalpha agonist gemfibrozil induces immune deviation and protects mice from EAE. We demonstrated that treatment with increases expression of Th2 transcription factor GATA-3 decreases Th1 T-bet vitro directly ex vivo. These changes correlated increase nuclear expression. Moreover, protective effects EAE were be partially dependent on IL-4 occur receptor-dependent manner. was demonstrated, first time, regulate IL-5 genes bind promoter presence steroid receptor coactivator-1, indicating can transactivate gene. Finally, administration ameliorated clinically established EAE, suggesting may provide option immune-mediated inflammatory diseases.