Genes Immun 2002 Apr;3(2):59-70
Natarajan C, Bright JJ.
Division of Neuroimmunology, Department of Neurology, Vanderbilt University School of Medicine, Nashville, TN 37212, USA.
Peroxisome proliferator-activated receptor-gamma (PPARgamma) is a nuclear receptor transcription factor that regulates adipocyte differentiation and glucose homeostasis.
PPARgamma agonists are potent therapeutic agents for the treatment of type 2 diabetes and obesity.
PPARgamma agonists also prevent inflammation in animal models, suggesting their use for the treatment of human inflammatory diseases.
Experimental allergic encephalomyelitis (EAE) is a Th1 cell-mediated inflammatory demyelinating disease model of multiple sclerosis (MS) and IL-12 plays a crucial role in the pathogenesis of EAE and MS.
In this study we have examined the effect of PPARgamma agonists on the pathogenesis of EAE.
In vivo treatment of SJL/J mice with PPARgamma agonists, 15-deoxyDelta(12,14) prostaglandin J(2) or Ciglitazone, decreased the duration and clinical severity of active immunization and adoptive transfer models of EAE.
PPARgamma agonists inhibited EAE in association with a decrease in IL-12 production and differentiation of neural antigen-specific Th1 cells.
In vitro treatment of activated T cells with PPARgamma agonists inhibited IL-12-induced activation of JAK-STAT signaling pathway and Th1 differentiation.
These findings highlight the fact that PPARgamma agonists regulate central nervous system inflammation and demyelination by inhibiting IL-12 production, IL-12 signaling and Th1 differentiation in EAE.