Inhibition of glial cell proinflammatory activities by peroxisome proliferator-activated receptor gamma agonist confers partial protection during antimyelin oligodendrocyte glycoprotein demyelination in vitro.
Details
Serval ID
serval:BIB_1CF21763FEAE
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Inhibition of glial cell proinflammatory activities by peroxisome proliferator-activated receptor gamma agonist confers partial protection during antimyelin oligodendrocyte glycoprotein demyelination in vitro.
Journal
Journal of Neuroscience Research
ISSN
0360-4012 (Print)
ISSN-L
0360-4012
Publication state
Published
Issued date
2003
Volume
71
Number
2
Pages
246-255
Language
english
Abstract
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.
Keywords
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
Pubmed
Web of science
Create date
24/01/2008 13:11
Last modification date
20/08/2019 12:53
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