Inhibition of glial cell proinflammatory activities by peroxisome proliferator-activated receptor gamma agonist confers partial protection during antimyelin oligodendrocyte glycoprotein demyelination in vitro.
Data(s) |
2003
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Resumo |
Peroxisome proliferator-activated receptor gamma (PPAR-gamma) is a member of the nuclear hormone superfamily originally characterized as a regulator of adipocyte differentiation and lipid metabolism. In addition, PPAR-gamma has important immunomodulatory functions. If the effect of PPAR-gamma's activation in T-cell-mediated demyelination has been recently demonstrated, nothing is known about the role of PPAR-gamma in antibody-induced demyelination in the absence of T-cell interactions and monocyte/macrophage activation. Therefore, we investigated PPAR-gamma's involvement by using an in vitro model of inflammatory demyelination in three-dimensional aggregating rat brain cell cultures. We found that PPAR-gamma was not constitutively expressed in these cultures but was strongly up-regulated following demyelination mediated by antibodies directed against myelin oligodendrocyte glycoprotein (MOG) in the presence of complement. Pioglitazone, a selective PPAR-gamma agonist, partially protected aggregates from anti-MOG demyelination. Heat shock responses and the expression of the proinflammatory cytokine tumor necrosis factor-alpha were diminished by pioglitazone treatment. Therefore, pioglitazone protection seems to be linked to an inhibition of glial cell proinflammatory activities following anti-MOG induced demyelination. We show that PPAR-gamma agonists act not only on T cells but also on antibody-mediated demyelination. This may represent a significant benefit in treating multiple sclerosis patients. |
Identificador |
http://serval.unil.ch/?id=serval:BIB_1CF21763FEAE isbn:0360-4012 (Print) pmid:12503087 doi:10.1002/jnr.10471 isiid:000180196500009 |
Idioma(s) |
en |
Fonte |
Journal of Neuroscience Research, vol. 71, no. 2, pp. 246-255 |
Palavras-Chave | #Analysis of Variance; Animals; Antibodies, Monoclonal/pharmacology; Astrocytes/drug effects; Astrocytes/metabolism; Cells, Cultured; Complement System Proteins/immunology; Crystallins/drug effects; Crystallins/metabolism; Demyelinating Diseases/chemically induced; Dose-Response Relationship, Drug; Drug Interactions; Embryo, Mammalian; Glyceraldehyde-3-Phosphate Dehydrogenases/genetics; Glyceraldehyde-3-Phosphate Dehydrogenases/metabolism; Heat-Shock Proteins/drug effects; Heat-Shock Proteins/metabolism; Heme Oxygenase (Decyclizing); Hypoglycemic Agents/pharmacology; Immunoglobulin G/pharmacology; Inflammation Mediators/physiology; Myelin Proteins; Myelin-Associated Glycoprotein/immunology; Myelin-Oligodendrocyte Glycoprotein; Neuroglia/drug effects; Neuroglia/physiology; Oxygenases; RNA, Messenger/biosynthesis; Rats; Receptors, Cytoplasmic and Nuclear/agonists; Receptors, Cytoplasmic and Nuclear/genetics; Reverse Transcriptase Polymerase Chain Reaction; Thiazoles/pharmacology; Thiazolidinediones; Transcription Factors/agonists; Transcription Factors/genetics; Tumor Necrosis Factor-alpha/drug effects; Tumor Necrosis Factor-alpha/metabolism; Up-Regulation |
Tipo |
info:eu-repo/semantics/article article |