Abstract
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).
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Alitretinoin
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Analysis of Variance
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Animals
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Cells, Cultured
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Cytokines / metabolism
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Dose-Response Relationship, Drug
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Drug Combinations
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Drug Interactions
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Encephalomyelitis, Autoimmune, Experimental / chemically induced
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Encephalomyelitis, Autoimmune, Experimental / complications
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Encephalomyelitis, Autoimmune, Experimental / drug therapy*
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Encephalomyelitis, Autoimmune, Experimental / physiopathology
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Enzyme-Linked Immunosorbent Assay / methods
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Immunization / methods
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Immunohistochemistry / methods
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Inflammation / chemically induced
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Inflammation / drug therapy
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Inflammation / etiology
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Ligands
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Lymph Nodes / cytology
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Lymph Nodes / drug effects
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Mice
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Mice, Transgenic
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Microglia / cytology
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Microglia / drug effects
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Myelin Basic Protein
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Nitric Oxide / metabolism
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Peptide Fragments / genetics
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Prostaglandin D2 / analogs & derivatives*
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Prostaglandin D2 / therapeutic use*
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RNA, Messenger / biosynthesis
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Receptors, Antigen, T-Cell, alpha-beta / genetics
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Receptors, Cytoplasmic and Nuclear / agonists*
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Receptors, Retinoic Acid / agonists*
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Retinoid X Receptors
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Reverse Transcriptase Polymerase Chain Reaction / methods
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Spleen / cytology
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Spleen / drug effects
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Time Factors
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Transcription Factors / agonists*
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Tretinoin / therapeutic use*
Substances
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15-deoxyprostaglandin J2
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Cytokines
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Drug Combinations
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Ligands
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Myelin Basic Protein
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Peptide Fragments
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RNA, Messenger
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Receptors, Antigen, T-Cell, alpha-beta
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Receptors, Cytoplasmic and Nuclear
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Receptors, Retinoic Acid
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Retinoid X Receptors
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T-cell receptor Vbeta 8.2
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Transcription Factors
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myelin basic protein Ac1-11(4Y)
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Alitretinoin
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Nitric Oxide
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Tretinoin
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Prostaglandin D2