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Peroxisome proliferator-activated receptor-gamma agonists inhibit experimental allergic encephalomyelitis by blocking IL-12 production, IL-12 signaling and Th1 differentiation

Genes & Immunity volume 3, pages 59–70 (2002)Cite this article

Abstract

Peroxisome proliferator-activated receptor-gamma (PPARγ) is a nuclear receptor transcription factor that regulates adipocyte differentiation and glucose homeostasis. PPARγ agonists are potent therapeutic agents for the treatment of type 2 diabetes and obesity. PPARγ 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 PPARγ agonists on the pathogenesis of EAE. In vivo treatment of SJL/J mice with PPARγ agonists, 15-deoxyΔ12,14 prostaglandin J2 or Ciglitazone, decreased the duration and clinical severity of active immunization and adoptive transfer models of EAE. PPARγ 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 PPARγ agonists inhibited IL-12-induced activation of JAK-STAT signaling pathway and Th1 differentiation. These findings highlight the fact that PPARγ agonists regulate central nervous system inflammation and demyelination by inhibiting IL-12 production, IL-12 signaling and Th1 differentiation in EAE.

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  1. Division of Neuroimmunology, Department of Neurology, Vanderbilt University School of Medicine, Nashville, 37212, TN, USA

    C Natarajan & J J Bright

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Correspondence to J J Bright.

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This work was supported in part by National Multiple Sclerosis Society Grant RG 3069A2/1 and national Institutes of Health Grant R01 NS42257-01A1 (to J J B).

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Natarajan, C., Bright, J. Peroxisome proliferator-activated receptor-gamma agonists inhibit experimental allergic encephalomyelitis by blocking IL-12 production, IL-12 signaling and Th1 differentiation. Genes Immun 3, 59–70 (2002). https://doi.org/10.1038/sj.gene.6363832

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