TNFalpha downregulates PPARdelta expression in oligodendrocyte progenitor cells: implications for demyelinating diseases.
TNFalpha has been implicated in several demyelinating disorders, including multiple sclerosis (MS) and X-adrenoleukodystrophy (X-ALD). TNFalpha 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, PPARdelta has been shown to promote oligodendrocyte (OL) survival and differentiation and PPARgamma has been implicated in inflammation. In the present study, we investigate on the effects of TNFalpha on OLs during differentiation in vitro. The results obtained show that TNFalpha treatment impairs PPARdelta expression with concomitant decrease of lignocerolyl-CoA synthase and very-long-chain fatty acid beta-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.
Cimini
Annamaria
A
Department of Basic and Applied Biology, Università di L'Aquila, Italy. cimini@univaq.it
Bernardo
Antonietta
A
Cifone
Maria Grazia
MG
Di Marzio
Luisa
L
Di Loreto
Silvia
S
Cifone
Grazia
G
Di Muzio
Luisa
L
D000818:Animals; D015153:Blotting, Western; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D002518:Ceramides / Q000378:metabolism; D003066:Coenzyme A Ligases / Q000378:metabolism; D016207:Cytokines / Q000494:pharmacology; D003711:Demyelinating Diseases / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D005227:Fatty Acids / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D005786:Gene Expression Regulation / Q000187:drug effects; D007371:Interferon-gamma / Q000494:pharmacology; D009836:Oligodendroglia / Q000166:cytology*; D010084:Oxidation-Reduction / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D002518:Ceramides; D016207:Cytokines; D005227:Fatty Acids; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D003066:Coenzyme A Ligases; C010210:lignoceric acid