Cytokine-induced cell death in human oligodendroglial cell lines:: I.: Synergistic effects of IFN-γ and TNF-α on apoptosis
Cytokine-induced cell death in human oligodendroglial cell lines:: I.: Synergistic effects of IFN-γ and TNF-α on apoptosis
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DOI：
10.1002/jnr.20118
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发表时间：
2004-06-15
影响因子：
4.2
通讯作者：
Ameloot, M
中科院分区：
文献类型：
--
作者：
Buntinx, M;Moreels, M;Ameloot, M
多发性硬化症是一种慢性中枢神经系统炎症性疾病。髓鞘和少突胶质细胞被认为是细胞免疫反应所致损伤的主要靶点。有间接证据表明，促炎症细胞因子，如肿瘤坏死因子-α和干扰素-γ，在多发性硬化症(MS)中可能具有促进疾病的作用。本研究分析了干扰素-γ和肿瘤坏死因子-α对人少突胶质细胞瘤(HOG)和MO3.13细胞的细胞毒作用。当少突胶质细胞系与干扰素-γ或肿瘤坏死因子-α共同培养时，两种细胞系在孵育24小时后均观察到凋亡细胞死亡。细胞凋亡表现为细胞存活率下降，细胞和细胞核形态发生凋亡性改变，细胞膜不对称性破坏。我们的数据显示，肿瘤坏死因子-α和干扰素-γ以剂量依赖的方式诱导两种少突胶质细胞系的凋亡，并且它们的协同作用导致细胞死亡增加。了解少突胶质细胞死亡途径的调节对于在MS(C)2004 Wiley-Liss，Inc.患者的损伤期间保护髓鞘产生细胞及其相关轴突至关重要。
Multiple sclerosis is a chronic inflammatory disease of the central nervous system. Myelin and oligodendrocytes are considered the major targets of injury caused by a cell-mediated immune response. There is circumstantial evidence that proinflammatory cytokines like tumor necrosis factor alpha (TNF-alpha) and interferon gamma (IFN-gamma) could have disease-promoting roles in multiple sclerosis (MS). In the present study, the cytotoxic effects of IFN-gamma and TNF-alpha on the human oligodendroglial cell lines human oligodendroglioma (HOG) and MO3.13 were analyzed. When the oligodendroglial cell lines were cultured in the presence of IFN-gamma or TNF-alpha, apoptotic cell death was observed in both cell lines after >24 hr incubation. Apoptosis was evidenced by a decrease in cell viability, apoptotic changes in cell and nucleus morphology, and disruption of the membrane asymmetry. Our data show that TNF-alpha and IFN-gamma induce apoptosis in a dose-dependent fashion in both oligodendroglial cell lines and that their synergistic effect results in enhanced cell death. Understanding the regulation of cell death pathways in oligodendrocytes is critical for protecting myelin-producing cells and their associated axons during injury in patients with MS. (C) 2004 Wiley-Liss, Inc.