Murphy G M, Lee Y L, Jia X C, Yu A C, Majewska A, Song Y, Schmidt K, Eng L F
Department of Psychiatry, Stanford University School of Medicine, CA 94305-5485, USA.
J Neurochem. 1995 Dec;65(6):2716-24. doi: 10.1046/j.1471-4159.1995.65062716.x.
Tumor necrosis factor-alpha is a pluripotent cytokine that is reportedly mitogenic to astrocytes. We examined expression of the astrocyte intermediate filament component glial fibrillary acidic protein in astrocyte cultures and the U373 glioblastoma cell line after treatment with tumor necrosis factor-alpha. Treatment with tumor necrosis factor-alpha for 72 h resulted in a decrease in content of glial fibrillary acidic protein and its encoding mRNA. At the same time, tumor necrosis factor-alpha treatment increased the expression of the cytokine interleukin-6 by astrocytes. The decrease in glial fibrillary acidic protein expression was greater when cells were subconfluent than when they were confluent. Thymidine uptake studies demonstrated that U373 cells proliferated in response to tumor necrosis factor-alpha, but primary neonatal astrocytes did not. However, in both U373 cells and primary astrocytes tumor necrosis factor-alpha induced an increase in total cellular protein content. Treatment of astrocytes and U373 cells for 72 h with the mitogenic cytokine basic fibroblast growth factor also induced a decrease in glial fibrillary acidic protein content and an increase in total protein level, demonstrating that this effect is not specific for tumor necrosis factor-alpha. The decrease in content of glial fibrillary acidic protein detected after tumor necrosis factor-alpha treatment is most likely due to dilution by other proteins that are synthesized rapidly in response to cytokine stimulation.
肿瘤坏死因子-α是一种多能细胞因子，据报道对星形胶质细胞有促有丝分裂作用。我们检测了用肿瘤坏死因子-α处理后，星形胶质细胞培养物和U373胶质母细胞瘤细胞系中星形胶质细胞中间丝成分胶质纤维酸性蛋白的表达。用肿瘤坏死因子-α处理72小时导致胶质纤维酸性蛋白及其编码mRNA的含量降低。同时，肿瘤坏死因子-α处理增加了星形胶质细胞细胞因子白细胞介素-6的表达。细胞未汇合时，胶质纤维酸性蛋白表达的降低比汇合时更明显。胸腺嘧啶核苷摄取研究表明，U373细胞对肿瘤坏死因子-α有增殖反应，但原代新生星形胶质细胞没有。然而，在U373细胞和原代星形胶质细胞中，肿瘤坏死因子-α均诱导细胞总蛋白含量增加。用促有丝分裂细胞因子碱性成纤维细胞生长因子处理星形胶质细胞和U373细胞72小时，也诱导了胶质纤维酸性蛋白含量降低和总蛋白水平升高，表明这种效应并非肿瘤坏死因子-α所特有。肿瘤坏死因子-α处理后检测到的胶质纤维酸性蛋白含量降低很可能是由于其他因细胞因子刺激而快速合成的蛋白质的稀释作用。
