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TNFα downregulates PPARδ expression in oligodendrocyte progenitor cells: Implications for demyelinating diseases
Author(s) -
Cimini Annamaria,
Bernardo Antonietta,
Cifone Grazia,
Di Muzio Luisa,
Di Loreto Silvia
Publication year - 2003
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.10143
Subject(s) - biology , multiple sclerosis , proinflammatory cytokine , oligodendrocyte , adrenoleukodystrophy , myelin , tumor necrosis factor alpha , peroxisome proliferator activated receptor , receptor , inflammation , downregulation and upregulation , progenitor cell , remyelination , peroxisome , microbiology and biotechnology , endocrinology , medicine , central nervous system , immunology , stem cell , biochemistry , gene
TNFα has been implicated in several demyelinating disorders, including multiple sclerosis (MS) and X‐adrenoleukodystrophy (X‐ALD). TNFα abundance is greatly increased in the areas surrounding damaged regions of the central nervous system of patients with MS and X‐ALD, but its role in the observed demyelination remains to be elucidated. A class of nuclear receptors, the peroxisome proliferator‐activated receptors (PPARs), has been implicated in several physiological and pathological processes. In particular, PPARδ has been shown to promote oligodendrocyte (OL) survival and differentiation and PPARγ has been implicated in inflammation. In the present study, we investigate on the effects of TNFα on OLs during differentiation in vitro. The results obtained show that TNFα treatment impairs PPARδ expression with concomitant decrease of lignocerolyl‐CoA synthase and very‐long‐chain fatty acid β‐oxidation as well as plasmalogen biosynthesis. We propose a hypothetical model possibly explaining the perturbation effects of proinflammatory cytokines on myelin synthesis, maturation, and turnover. GLIA 41:3–14, 2003. © 2003 Wiley‐Liss, Inc.