TUMOR-NECROSIS-FACTOR-ALPHA MEDIATES THE RELEASE OF BIOACTIVE TRANSFORMING GROWTH-FACTOR-BETA IN MURINE MICROGLIAL CELL-CULTURES
TUMOR-NECROSIS-FACTOR-ALPHA MEDIATES THE RELEASE OF BIOACTIVE TRANSFORMING GROWTH-FACTOR-BETA IN MURINE MICROGLIAL CELL-CULTURES
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DOI：
10.1006/clin.1995.1163
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发表时间：
1995-12-01
期刊：
影响因子：
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通讯作者：
PETERSON, PK
中科院分区：
文献类型：
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作者：
CHAO, CC;HU, SX;PETERSON, PK
已经提出由神经胶质细胞产生的肿瘤坏死因子（TNF）-α和转化生长因子（TGF）-β在各种神经退行性疾病中起作用。然而，这两种细胞因子的相互作用是未知的。我们测试了这样的假设，即从脂多糖（LPS）处理的小鼠小胶质细胞释放的TNF-α会刺激TGF-β的释放，这反过来又会控制TNF-α的产生。用LPS处理鼠小胶质细胞培养物导致TNF-α的急性释放（8小时达到峰值），随后是生物活性TGF-β的延迟释放（8小时达到峰值）。抗TNF-α抗体显著抑制LPS刺激的TGF-β产生，表明TNF-α参与TGF-β产生。此外，外源性TNF-α以剂量依赖性方式诱导小胶质细胞表达TGF-β 1 mRNA和释放TGF-β。另一方面，外源性TGF-β抑制LPS刺激的TNF-α释放。这些发现表明，TGF-β对小胶质细胞TNF-α的产生具有自动调节作用，这可能会限制炎症相关的脑损伤。(C)出版社：Academic Press
Tumor necrosis factor (TNF)-alpha and transforming growth factor (TGF)-beta produced by glial cells have been proposed to play a role in various neurodegenerative diseases. The interaction of these two cytokines, however, is unknown. We tested the hypothesis that the TNF-alpha released from lipopolysaccharide (LPS)-treated murine microglial cells would stimulate the release of TGF-beta, which in turn would control TNF-alpha production. Treatment of murine microglial cell cultures with LPS resulted in an acute release of TNF-alpha (peak by 8 hr) followed by delayed release of bioactive TGF-beta (peak by 8 hr). Anti-TNF-alpha antibody significantly inhibited LPS-stimulated TGF-beta production, suggesting the involvement of TNF-alpha in TGF-beta production. Also, exogenous TNF-alpha induced in a dose-dependent fashion microglial cell expression of TGF-beta 1 mRNA and release of TGF-beta. Exogenous TGF-beta, on the other hand, suppressed LPS-stimulated TNF-alpha release. These findings suggest an autoregulation of microglial cell TNF-alpha production by TGF-beta which may limit inflammation-associated brain injury. (C) 1995 Academic Press, Inc.