活化的T淋巴细胞可诱导小胶质细胞产生肿瘤坏死因子-α。极迟抗原-4的参与及β-1b干扰素的抑制作用。
Microglial production of TNF-alpha is induced by activated T lymphocytes. Involvement of VLA-4 and inhibition by interferonbeta-1b.
作者信息
Chabot S, Williams G, Yong V W
机构信息
Neuroimmunology Unit, Department of Neurology and Neurosurgery, McGill University, Montreal Neurological Institute, Montreal, Quebec, Canada H3A 2B4.
出版信息
J Clin Invest. 1997 Aug 1;100(3):604-12. doi: 10.1172/JCI119571.
Abstract
TNF-alpha is a proinflammatory cytokine involved in many inflammatory conditions such as Crohn's disease, rheumatoid arthritis, cachexia, AIDS, and multiple sclerosis (MS). TNF-alpha is produced mainly by cells of the macrophage lineage, which includes microglia in the central nervous system. Here, we describe a mechanism through which TNF-alpha is generated by microglia. We show that activated human T lymphocytes induce the microglial production of TNF-alpha, and that is attenuated by a functional blocking antibody to CD49d, the alpha chain of the VLA-4 integrin on T cells. We also report that interferonbeta-1b (IFNbeta-1b), a drug that alleviates symptoms in MS, downregulates the expression of CD49d and reduces TNF-alpha production, mechanisms which can help account for its efficacy in MS.
摘要
肿瘤坏死因子-α（TNF-α）是一种促炎细胞因子，参与多种炎症性疾病，如克罗恩病、类风湿性关节炎、恶病质、艾滋病和多发性硬化症（MS）。TNF-α主要由巨噬细胞谱系的细胞产生，其中包括中枢神经系统中的小胶质细胞。在此，我们描述了一种小胶质细胞产生TNF-α的机制。我们发现活化的人T淋巴细胞可诱导小胶质细胞产生TNF-α，而针对T细胞上VLA-4整合素α链CD49d的功能性阻断抗体可减弱这种诱导作用。我们还报告称，干扰素β-1b（IFNβ-1b），一种可缓解MS症状的药物，可下调CD49d的表达并减少TNF-α的产生，这些机制有助于解释其在MS中的疗效。
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