QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Racke, M. K. Articles by Lovett-Racke, A. E. Search for Related Content PubMed PubMed Citation Articles by Racke, M. K. Articles by Lovett-Racke, A. E.

---

Symposium: Nutrients, Nuclear Receptors, Inflammation, and Immunity

Nuclear Receptors and Autoimmune Disease: The Potential of PPAR Agonists to Treat Multiple Sclerosis^1,2

Michael K. Racke^*,,3, Anne R. Gocke^*, Mark Muir^*, Asim Diab^*, Paul D. Drew^** and Amy E. Lovett-Racke^*

^* Department of Neurology and the Center for Immunology, University of Texas Southwestern Medical Center, Dallas, TX 75390 and ^** Department of Neurobiology and Developmental Sciences, University of Arkansas for the Medical Sciences, Little Rock, AR 72205

³ To whom correspondence should be addressed. E-mail: michael.racke{at}utsouthwestern.edu.

Experimental autoimmune encephalomyelitis (EAE) is a T-cell–mediated, autoimmune disorder characterized by central nervous system inflammation and demyelination, features reminiscent of the human disease, multiple sclerosis (MS). Prior work in the EAE model has suggested that encephalitogenic T cells are of the T helper (Th)-1 phenotype. Our group has performed several studies in the EAE model that suggest that a strategy for treating autoimmune disorders is to convert the pathogenic cells from the Th1 to Th2 phenotype. Peroxisome proliferator-activated receptors (PPARs) are members of a nuclear hormone receptor superfamily that include receptors for steroids, retinoids, and thyroid hormone, all of which are known to affect the immune response. Recently, we examined the role of PPAR in EAE and observed that administration of the PPAR agonist 15-deoxy-^12,14 prostaglandin J2 exerted a significant therapeutic effect predominantly by inhibiting the activation and expansion of encephalitogenic T cells. One potential advantage in studying PPAR agonists is that they have been very well tolerated when used in humans to treat conditions such as elevated triglycerides. Building on prior work in immune deviation and with PPAR agonists, we have demonstrated that PPAR agonists can alter the cytokine phenotype of myelin-reactive T cells, alter their encephalitogenicity, and be useful in the treatment of EAE. The fact that PPAR agonists have been used as therapeutic agents in humans to treat metabolic conditions for over 25 years with little toxicity makes them attractive candidates for use as adjunctive therapies in MS.

KEY WORDS: • PPAR • autoimmunity • multiple sclerosis • cytokines • nuclear receptors