Cytokines and the molecular mechanisms of alcoholic liver disease
Cytokines and the molecular mechanisms of alcoholic liver disease
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DOI：
10.1111/j.1530-0277.1999.tb04662.x
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发表时间：
1999-09-01
影响因子：
3.2
通讯作者：
Diehl, AM
中科院分区：
文献类型：
--
作者：
Diehl, AM
这份手稿是在1999年7月酒精中毒研究会年会上作为全体讲座发表的。它描述了损伤相关细胞因子肿瘤坏死因子α促进肝再生的一般机制，然后详细说明了慢性酒精消费如何抑制肿瘤坏死因子启动的肝营养信号。有证据表明，慢性酒精暴露会损害依赖肿瘤坏死因子激活的应激激活蛋白激酶及其一些靶标，包括生长刺激DNA结合蛋白c-jun。酒精暴露还会阻止肿瘤坏死因子激活再生肝细胞中氧化还原敏感的转录因子--核因子-kappaB。紧随其后的是肝细胞增殖减少，以及肝脏中肿瘤坏死因子调节的生存因子(如Bclxl)的诱导受阻。因此，慢性酒精摄入可能会通过抑制肿瘤坏死因子α和其他生长调节细胞因子的养肝和护肝作用来损害肝脏。
This manuscript was given as a plenary lecture at the annual meeting of the Research Society on Alcoholism in July of 1999. It describes the general mechanisms by which tumor necrosis factor (TNF) alpha, an injury-related cytokine, promotes liver regeneration and then details how TNF-initiated hepatotrophic signals are inhibited by chronic ethanol consumption. There is evidence that chronic ethanol exposure impairs the TNF-dependent activation of stress-activated protein kinases and some of their targets, including the growth-stimulatory DNA binding protein, c-Jun. Ethanol exposure also prevents TNF from activating the redox-sensitive transcription factor, NF kappa B, in regenerating hepatocytes. These effects are followed by decreased hepatocyte proliferation, as well as by impaired induction of TNF-regulated survival factors, such as Bcl-xL, in the liver. Thus, chronic ethanol consumption may damage the liver by inhibiting the hepatotrophic and hepatoprotective actions of TNF alpha and other growth-regulatory cytokines.