Molecular mechanisms of alcoholic liver disease: innate immunity and cytokines.
Molecular mechanisms of alcoholic liver disease: innate immunity and cytokines.
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DOI：
10.1111/j.1530-0277.2010.01399.x
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发表时间：
2011-05
期刊：
影响因子：
--
通讯作者：
Gao B
中科院分区：
文献类型：
--
作者：
Miller AM;Horiguchi N;Jeong WI;Radaeva S;Gao B
饮酒是全球慢性肝病发病机制中的一个主要病因，可导致脂肪肝、酒精性肝炎、纤维化/肝硬化以及肝细胞癌。在过去几十年中，我们对酒精性肝损伤的分子机制的理解取得了重大进展。固有免疫成分如枯否细胞、脂多糖/ toll样受体4以及补体在酒精暴露下被激活，在酒精性肝病（ALD）的发生和发展中起关键作用。脂多糖激活枯否细胞还会产生白细胞介素 - 6（IL - 6）和白细胞介素 - 10（IL - 10），它们可能在改善酒精性肝病中起保护作用。IL - 6激活肝细胞和肝窦内皮细胞中的信号转导和转录激活因子3（STAT3），而IL - 10激活枯否细胞/巨噬细胞中的STAT3，从而预防酒精性肝病。此外，饮酒还会抑制固有免疫的一些成分，如自然杀伤（NK）细胞，这是一种在肝脏抗病毒、抗肿瘤和抗纤维化防御中起关键作用的细胞。乙醇对NK细胞的抑制可能在酒精性肝病的发病机制中起重要作用。了解固有免疫和细胞因子在酒精性肝损伤中的作用可能为酒精性肝病的治疗提供新的治疗靶点的思路。
Alcohol consumption is a predominant etiological factor in the pathogenesis of chronic liver diseases worldwide, causing fatty liver, alcoholic hepatitis, fibrosis/cirrhosis, and hepatocellular carcinoma. In the past few decades, significant progress has been made in our understanding of the molecular mechanisms underlying alcoholic liver injury. Activation of innate immunity components such as Kupffer cells, LPS/TLR4, and complements in response to alcohol exposure plays a key role in the development and progression of alcoholic liver disease (ALD). LPS activation of Kupffer cells also produces IL-6 and IL-10 that may play a protective role in ameliorating ALD. IL-6 activates signal transducer and activator of transcription 3 (STAT3) in hepatocytes and sinusoidal endothelial cells, while IL-10 activates STAT3 in Kupffer cells/macrophages, subsequently protecting against ALD. In addition, alcohol consumption also inhibits some components of innate immunity such as natural killer (NK) cells, a type of cells that play key roles in anti-viral, anti-tumor, and anti-fibrotic defenses in the liver. Ethanol inhibition of NK cells likely contributes significantly to the pathogenesis of ALD. Understanding the roles of innate immunity and cytokines in alcoholic liver injury may provide insight into novel therapeutic targets in the treatment of alcoholic liver disease.
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酒精性肝病临床进展的当前实验观点。
DOI：
10.1111/j.1530-0277.2009.01015.x
发表时间：
2009-10
期刊：
Alcoholism, clinical and experimental research
影响因子：
--
作者：
Breitkopf K;Nagy LE;Beier JI;Mueller S;Weng H;Dooley S
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Dooley S
影响因子：
13.5
作者：
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Ju, Cynthia
Toll样受体4的肝硬化预测单核苷酸多态性与肝星状细胞反应的功能联系。
影响因子：
13.5
作者：
Guo, Jinsheng;Loke, Johnny;Zheng, Feng;Hong, Feng;Yea, Steven;Fukata, Masayuki;Tarocchi, Mirko;Abar, Olivia T.;Huang, Hongjin;Sninsky, John J.;Friedman, Scott L.
通讯作者：
Friedman, Scott L.
影响因子：
2.3
作者：
Gao, B
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Gao, B
影响因子：
13.5
作者：
Hong, F;Radaeva, S;Gao, B
通讯作者：
Gao, B