Interferon-beta is neuroprotective against the toxicity induced by activated microglia.
Interferon-beta is neuroprotective against the toxicity induced by activated microglia.
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发表时间：
2007
期刊：
影响因子：
2.9
通讯作者：
Shijie Jin;J. Kawanokuchi;T. Mizuno;Jinyan Wang;Yoshifumi Sonobe;H. Takeuchi;A. Suzumura
中科院分区：
文献类型：
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作者：
Shijie Jin;J. Kawanokuchi;T. Mizuno;Jinyan Wang;Yoshifumi Sonobe;H. Takeuchi;A. Suzumura
多发性硬化症（MS）是一种慢性中枢神经系统炎症性疾病，以脱髓鞘、T淋巴细胞浸润和神经元变性为特征。干扰素- β (IFN)- β可减轻多发性硬化复发缓解型的症状。在本研究中，我们研究了IFN- β是否对皮质神经元和小胶质细胞共培养中活化的小胶质细胞诱导的毒性具有神经保护作用。ifn - β将激活的小胶质细胞的谷氨酸和超氧化物的产生分别抑制到脂多糖刺激的70%和75%，并防止小胶质细胞诱导的神经元细胞死亡。虽然ifn - β增强了激活的小胶质细胞产生肿瘤坏死因子(TNF)- α、白细胞介素(IL)-1 β和一氧化氮（NO），但这些分子并不直接诱导培养的皮质神经元的神经毒性。ifn - β不能阻止过氧亚硝酸盐供体3- morpholinosydnon亚胺（sin1）或嗜离子性谷氨酸受体激动剂如n -甲基- d -天冬氨酸（NMDA）和α -氨基-3-羟基-5-甲基-4-异恶唑丙酸（AMPA）诱导的神经元细胞死亡。这些结果表明ifn - β可能是一种有效的药物，可以对抗与激活的小胶质细胞相关的神经毒性。
Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system characterized by demyelination, T lymphocyte infiltration, and neuronal degeneration. Interferon-beta (IFN)-beta reduces symptoms of the relapsing-remitting form of MS. In this study, we investigated whether IFN-beta is neuroprotective against the toxicity induced by activated microglia in cortical neurons and microglia co-cultures. IFN-beta suppressed the production of glutamate and superoxide by activated microglia to 70% and 75% of lipopolysaccharide stimulation, respectively, and prevented microglial-induced neuronal cell death. Although IFN-beta enhanced the production of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, and nitric oxide (NO) by activated microglia, these molecules did not directly induce neurotoxicity in cultured cortical neurons. IFN-beta did not prevent neuronal cell death induced by the peroxynitrite donor 3-morpholinosydnonimine (SIN-1) or ionotropic glutamate receptor agonists such as N-methyl-D-aspartic acid (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA). These results suggest that IFN-beta may be a useful agent counteracting neurotoxicity associated with activated microglia.