Liver X receptor activation decreases the severity of experimental autoimmune encephalomyelitis.
Agonists of liver X receptors (LXR), members of the nuclear hormone receptor superfamily, alter secretion of proinflammatory cytokines, suggesting potential antiinflammatory effects. A synthetic LXR agonist inhibited T-cell proliferation and cytokine release in a dose-dependent manner. Treatment of mice during induction of experimental autoimmune encephalomyelitis reduced clinical symptoms, central nervous system cellular inflammation, and major histocompatibility class II expression on microglia, as well as demyelination. In contrast to in vitro analysis, no reductions in peripheral neuroantigen specific T-cell responses were detected in comparing ligand and vehicle treated mice. These data suggest that LXR agonists play an important protective role in the regulation of T-cell-mediated inflammatory disease of the central nervous system.
Hindinger
Claudia
C
Department of Neurology, University of Southern California, Keck School of Medicine, Los Angeles, California, USA.
Hinton
David R
DR
Kirwin
Stefanie J
SJ
Atkinson
Roscoe D
RD
Burnett
Margaret E
ME
Bergmann
Cornelia C
CC
Stohlman
Stephen A
SA
D000818:Animals; D015704:CD4 Antigens / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000819:agonists*; D004305:Dose-Response Relationship, Drug; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000473:pathology* / Q000517:prevention & control*; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression / Q000187:drug effects; D005802:Genes, MHC Class II / Q000235:genetics; D006845:Hydrocarbons, Fluorinated; D008024:Ligands; D000071518:Liver X Receptors; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D057093:Orphan Nuclear Receptors; D010047:Ovalbumin / Q000276:immunology / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013449:Sulfonamides / Q000494:pharmacology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D005466:Fluorocarbons; D000096926:Benzenesulfonamides
D015704:CD4 Antigens; D004268:DNA-Binding Proteins; D006845:Hydrocarbons, Fluorinated; D008024:Ligands; D000071518:Liver X Receptors; D057093:Orphan Nuclear Receptors; D010047:Ovalbumin; D018160:Receptors, Cytoplasmic and Nuclear; D013449:Sulfonamides; C423915:T0901317; D005466:Fluorocarbons; D000096926:Benzenesulfonamides