Interferon-β is neuroprotective against the toxicity induced by activated microglia
Interferon-β is neuroprotective against the toxicity induced by activated microglia
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DOI：
10.1016/j.brainres.2007.08.055
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发表时间：
2007-11-07
期刊：
影响因子：
2.9
通讯作者：
Suzumura, Akio
中科院分区：
文献类型：
--
作者：
Jin, Shijie;Kawanokuchi, Jun;Suzumura, Akio
多发性硬化症(MS)是一种慢性中枢神经系统炎症性疾病，以髓鞘脱落、T淋巴细胞浸润和神经元变性为特征。干扰素-β可减轻复发缓解型多发性硬化症的症状。在本研究中，我们研究了干扰素-β对皮质神经元和小胶质细胞共培养中激活的小胶质细胞诱导的毒性是否具有神经保护作用。干扰素-β抑制激活的小胶质细胞产生谷氨酸和超氧化物。分别对70%和75%的脂多糖刺激，并防止小胶质细胞包括神经细胞的死亡。尽管干扰素-β可促进激活的小胶质细胞产生肿瘤坏死因子-α、白介素1-β和一氧化氮，但这些分子并不直接对培养的皮质神经元产生神经毒性。干扰素-β不能阻止过氧亚硝酸供体3-吗啉-天冬氨酸亚胺(SIN-1)或N-甲基-D-天冬氨酸(N-甲基-D-天冬氨酸)和alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic酸(AMPA)等离子亲和性谷氨酸受体激动剂诱导的神经细胞死亡。这些结果表明，干扰素-β可能是一种有用的药物，对抗与激活的小胶质细胞相关的神经毒性。(C)2007 Elsevier B.V.保留所有权利。
Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system characterized by clemyelination, T lymphocyte infiltration, and neuronal degeneration. lnterferon-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-incluced neuronal cell death. Although IFN-beta enhanced the production of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, 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. (c) 2007 Elsevier B.V. All rights reserved.