Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0014070 (encephalomyelitis)
 13,017 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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 J2 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.
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PMID:Peroxisome proliferator-activated receptor-gamma agonists inhibit experimental allergic encephalomyelitis by blocking IL-12 production, IL-12 signaling and Th1 differentiation. 1196 Mar 3

Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) is a member of the nuclear-receptor superfamily that binds to DNA with retinoid X receptors (RXRs) as PPAR-RXR heterodimers. In experimental autoimmune encephalomyelitis (EAE), the gene expression of PPAR-gamma was demonstrated in spinal cord during the course of EAE. Administration of 15-deoxy-(12,14)-prostaglandin J2 (15d-PGJ2) or 9-cis-retinoic acid (RA) alone at the onset of clinical signs of EAE reduced the severity of disease, however, their combination resulted in enhanced amelioration of disease. These results suggest that use of RXR specific ligands may be highly effective when combined with PPAR-gamma agonists in the treatment of autoimmune demyelinating diseases such as multiple sclerosis (MS).
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PMID:Ligands for the peroxisome proliferator-activated receptor-gamma and the retinoid X receptor exert additive anti-inflammatory effects on experimental autoimmune encephalomyelitis. 1497 92

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 PPARgamma in EAE and observed that administration of the PPARgamma agonist 15-deoxy-Delta(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 PPARalpha 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 PPARalpha 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 PPARalpha 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.
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PMID:Nuclear receptors and autoimmune disease: the potential of PPAR agonists to treat multiple sclerosis. 1648 46