Cytokine-mediated neuronal apoptosis
Cytokine-mediated neuronal apoptosis
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DOI：
10.1016/s0197-0186(96)00078-2
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发表时间：
1997-04-01
影响因子：
4.2
通讯作者：
Chao, CC
中科院分区：
文献类型：
--
作者：
Hu, S;Peterson, PK;Chao, CC
据报道，细胞因子可通过自由基一氧化氮 (NO) 诱导神经元损伤；然而，细胞因子介导的神经毒性的确切机制尚不清楚。我们研究了这样的假设：人类胎儿神经元原代培养物中细胞因子介导的神经毒性是通过 NO 触发的细胞凋亡机制发生的。用干扰素 (IFN)-γ 加白细胞介素 (IL)-1 β 处理混合神经元/神经胶质细胞培养物 13 天，诱导高 NO 输出，并伴有明显的神经元损失。 NO 合酶抑制剂 N-单甲基-L-精氨酸 (NMMA) 显着减轻细胞因子诱导的神经元损失，证实了 NO 的参与。细胞因子介导的神经元损伤伴随着形态学变化和与细胞凋亡一致的DNA断裂模式。用 NMMA 处理神经细胞培养物可防止细胞因子介导的细胞凋亡。这些使用原代人类神经元细胞培养物的发现支持这样的假设：细胞因子介导的涉及 NO 的神经毒性通过细胞凋亡机制进行。这些发现可能会导致针对涉及神经胶质细胞、细胞因子和 NO 的神经退行性疾病的新疗法的开发。 (C) 1997 爱思唯尔科学有限公司。
Cytokines have been reported to induce neuronal injury via the free radical nitric oxide (NO); however, the precise mechanism underlying cytokine-mediated neurotoxicity is unclear. We investigated the hypothesis that cytokine-mediated neurotoxicity in primary cultures of human fetal neurons occurs via an apoptotic mechanism triggered by NO. Treatment of mixed neuronal/glial cell cultures with interferon (IFN)-gamma plus interleukin (IL)-1 beta for 13 days induced a high output of NO accompanied by marked neuronal loss. The NO synthase inhibitor N-monomethyl-L-arginine (NMMA) significantly attenuated cytokine-induced neuronal loss, confirming the involvement of NO. Cytokine-mediated neuronal injury was accompanied by morphologic changes and a DNA fragmentation pattern consistent with apoptosis. Treatment of neuronal cell cultures with NMMA protected against cytokine-mediated apoptotic death. These findings, using primary human neuronal cell cultures, support the hypothesis that cytokine-mediated neurotoxicity involving NO proceeds via an apoptotic mechanism. These findings could lead to the development of new therapies for neurodegenerative diseases involving glia, cytokines, and NO. (C) 1997 Elsevier Science Ltd.