Cytokine effects on glutamate uptake by human astrocytes
Cytokine effects on glutamate uptake by human astrocytes
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DOI：
10.1159/000026433
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发表时间：
2000-01-01
影响因子：
2.4
通讯作者：
Chao, SC
中科院分区：
文献类型：
--
作者：
Hu, SX;Sheng, WS;Chao, SC
星形胶质细胞摄取谷氨酸被认为在脑部炎症过程中起到神经保护作用。利用原代培养的人胎儿星形胶质细胞，我们研究了选定的细胞因子对谷氨酸摄取活性的影响。白介素1β和肿瘤坏死因子受体呈剂量依赖性地抑制星形胶质细胞谷氨酸摄取，而干扰素(干扰素)-γ单独刺激这一活性。一氧化氮合酶抑制剂N-G-单甲基-L-精氨酸可阻断IL-1β介导的谷氨酸摄取抑制作用，提示一氧化氮参与了IL-1β的作用。IL-1受体拮抗剂蛋白可完全逆转细胞因子的抑制作用，提示IL-1β具有重要作用。抗炎细胞因子干扰素-β阻断了细胞因子(IL-1β加干扰素-γ)诱导的谷氨酸摄取抑制，并相应减少了一氧化氮的生成。综上所述，这些发现表明，促炎细胞因子通过涉及一氧化氮的机制抑制星形胶质细胞谷氨酸的摄取，而干扰素-β可能通过阻断细胞因子诱导的一氧化氮在脑炎性疾病中发挥有益的治疗作用。版权所有(C)2000 S.Karger AG，巴塞尔。
Glutamate uptake by astrocytes has been postulated to play a neuroprotective role during brain inflammation. Using primary human fetal astrocyte cultures, we investigated the influence of selected cytokines on glutamate uptake activity. Interleukin (IL)-1 beta and tumor necrosis factor-tr dose-dependently inhibited astrocyte glutamate uptake, whereas interferon (IFN)-gamma alone stimulated this activity. The nitric oxide synthase inhibiter, N-G-monomethyl-L-arginine, blocked IL-1 beta-mediated inhibition of glutamate uptake, suggesting involvement of nitric oxide in the effect of IL-1 beta. IL-1 receptor antagonist protein totally reversed the inhibitory effect of cytokines, suggesting a critical role of IL-1 beta. The anti-inflammatory cytokine IFN-beta blocked cytokine (IL-1 beta plus IFN-gamma)-induced inhibition of glutamate uptake with a corresponding reduction in nitric oxide generation. Taken together, these findings suggest that proinflammatory cytokines inhibit astrocyte glutamate uptake by a mechanism involving nitric oxide, and that IFN-beta may exert a therapeutically beneficial effect by blocking cytokine-induced nitric oxide production in inflammatory diseases of the brain. Copyright (C) 2000 S. Karger AG, Basel.