TNFα downregulates PPARδ expression in oligodendrocyte progenitor cells:: Implications for demyelinating diseases
TNFα downregulates PPARδ expression in oligodendrocyte progenitor cells:: Implications for demyelinating diseases
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DOI：
10.1002/glia.10143
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发表时间：
2003-01-01
期刊：
影响因子：
6.2
通讯作者：
Di Loreto, S
中科院分区：
文献类型：
--
作者：
Cimini, A;Bernardo, A;Di Loreto, S
TNF α与几种脱髓鞘疾病有关，包括多发性硬化症（MS）和X-肾上腺脑白质营养不良（X-ALD）。在MS和X-ALD患者的中枢神经系统受损区域周围区域，TNF α丰度大大增加，但其在观察到的脱髓鞘中的作用仍有待阐明。一类核受体，过氧化物酶体增殖物激活受体（PPARdelta），已涉及在几个生理和病理过程。特别地，PPARdelta已显示促进少突胶质细胞（OL）存活和分化，而PPARgamma与炎症有关。在本研究中，我们研究了在体外分化过程中TNF α对OLs的影响。所获得的结果显示TNF α处理损害了PPARdelta表达，伴随着木质蜡酰辅酶A合酶和极长链脂肪酸β-氧化以及缩醛磷脂生物合成的降低。我们提出了一个假设的模型，可能解释的扰动影响的促炎细胞因子对髓鞘合成，成熟和营业额。(C)2003 Wiley-Liss，Inc.
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 (PPARdelta), 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. (C) 2003 Wiley-Liss, Inc.