Role of interleukin-1β in hypoxia-induced depression of glutamate uptake in retinal Muller cells
Role of interleukin-1β in hypoxia-induced depression of glutamate uptake in retinal Muller cells
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DOI：
10.1007/s00417-013-2516-z
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发表时间：
2014-01-01
影响因子：
2.7
通讯作者：
Shen, Xi
中科院分区：
文献类型：
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作者：
Chen, Chongda;Chen, Hui;Shen, Xi
提示缺氧缺血性视网膜疾病可引起视网膜神经节细胞的丢失。过量的谷氨酸释放参与这些条件。穆勒细胞的主要功能是调节谷氨酸水平，但在这些疾病中，该功能受到损害。为探讨白细胞介素-1 β（IL-1 β）对缺氧状态下视网膜Muller细胞谷氨酸摄取的影响及其可能机制，采用Western blotting和实时荧光定量RT-PCR方法检测缺氧状态下视网膜Muller细胞IL-1 β、Kir4.1和GLAST的表达水平，并采用谷氨酸摄取实验检测GLAST的活性。在常氧条件下用IL-1 β处理后，研究了这些蛋白（Kir4.1和GLAST）及其mRNA，以及Muller细胞中的谷氨酸摄取活性。为证实IL-1 β对Muller细胞谷氨酸摄取活性的影响，采用IL-1 ra对Muller细胞谷氨酸摄取活性的影响进行了研究，结果表明，缺氧条件下，Muller细胞谷氨酸摄取、Kir4.1和GLAST表达均显著降低，而IL-1 β表达则显著升高。IL-1 β处理诱导正常氧下视网膜Muller细胞谷氨酸摄取抑制，Kir4.1和GLAST表达减少。IL-1 ra可显著改善缺氧条件下视网膜Muller细胞Kir4.1和GLAST表达的下降及谷氨酸摄取活性的降低，提示炎症细胞因子IL-1 β可诱导缺氧条件下视网膜Muller细胞Kir4.1和GLAST表达的下降及谷氨酸摄取活性的降低。
It is suggested that hypoxic-ischemic retinal diseases induce loss of retinal ganglion cells. Excess glutamate release is involved in these conditions. A predominant function of Muller cells is to regulate glutamate levels, but in these diseases the function is compromised. The present study was performed to investigate the role of interleukin-1 beta(IL-1 beta)on the glutamate uptake in retinal Muller cells under hypoxia and to study the possible mechanism.The levels of IL-1 beta,Kir4.1, and GLAST in retinal Muller cells under hypoxia were analyzed by Western blotting and realtime-RT-PCR, and glutamate uptake assay was undertaken to investigate the activity of GLAST. After being treated with IL-1 beta under normoxia, these proteins (Kir4.1 and GLAST) and their mRNAs, and glutamate uptake activity in Muller cells were investigated. To confirm the effect of IL-1 beta on glutamate uptake activity in Muller cells, addition of IL-1ra was used.Under hypoxia, Muller cells glutamate uptake, Kir4.1 and GLAST expressions were decreased significantly; however, IL-1 beta expression was increased. IL-1 beta treatment induced depression of glutamate uptake, decrease of Kir4.1 and GLAST expressions in retinal Muller cells under normoxia. Moreover, addition of IL-1ra significantly ameliorated decreases in Kir4.1 and GLAST expressions, and compromise of glutamate uptake activity in retinal Muller cells under hypoxia.These findings indicated that decreases in Kir4.1 and GLAST expressions and depression of glutamate uptake in retinal Muller cells under hypoxia may be induced by the inflammatory cytokine IL-1 beta.