Microglial production of TNF-alpha is induced by activated T lymphocytes - Involvement of VLA-4 and inhibition by interferon beta-1b
Microglial production of TNF-alpha is induced by activated T lymphocytes - Involvement of VLA-4 and inhibition by interferon beta-1b
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DOI：
10.1172/jci119571
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发表时间：
1997-08-01
影响因子：
15.9
通讯作者：
Yong, VW
中科院分区：
文献类型：
--
作者：
Chabot, S;Williams, G;Yong, VW
tnf - α是一种促炎细胞因子，参与许多炎症疾病，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主要由巨噬细胞系的细胞产生，其中包括中枢神经系统的小胶质细胞。在这里，我们描述了小胶质细胞产生tnf - α的机制。我们发现，活化的人T淋巴细胞诱导小胶质细胞产生tnf - α，并被T细胞上VLA-4整合素的α链CD49d的功能性阻断抗体减弱。我们还报道了干扰素β -1b (IFN β -1b)，一种缓解MS症状的药物，下调CD49d的表达并减少tnf - β的产生，这有助于解释其在MS中的疗效。
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 interferon beta-1b (IFN beta-1b), a drug that alleviates symptoms in MS, downregulates the expression of CD49d and reduces TNF-beta production, mechanisms which can help account for its efficacy in MS.