Signalling pathways in alcohol-induced liver inflammation.
Signalling pathways in alcohol-induced liver inflammation.
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DOI：
10.1016/j.jhep.2009.03.007
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发表时间：
2009-06
影响因子：
25.7
通讯作者：
Szabo G
中科院分区：
文献类型：
--
作者：
Mandrekar P;Szabo G
酒精性肝损伤的发病机制涉及肝脏不同细胞类型中几种细胞内信号通路的相互作用。酒精诱导的肝巨噬细胞对门静脉内毒素/脂多糖（LPS）的敏感性被认为是酒精性肝病（ALD）的标志。与LPS诱导的信号转导相关的细胞内机制在酒精性肝损伤的发生和发展中起着至关重要的作用，并且正在被广泛探索。LPS被肝脏中巨噬细胞和其他细胞类型上的Toll样受体4（TLR 4）识别，下游信号传导途径的激活最终导致转录因子如NFκB、AP-1的激活，导致ALD中炎性细胞因子产生增加。此外，LPS诱导的MAPK如ERK和p38也有助于肝损伤。在巨噬细胞中，酒精诱导的活性氧及其与TLR通路的相互作用导致炎症的重要性正变得越来越明显。总的来说，这些信号通路诱导促炎和抗炎细胞因子，在ALD中发挥重要作用。在这篇综述中，我们描述了导致酒精性肝病中酒精诱导的炎症的关键信号中间体。
The pathogenesis of alcoholic liver injury involves interactions of several intracellular signalling pathways in different cell types of the liver. Alcohol-induced sensitization of liver macrophages to portal endotoxin/lipopolysaccharide (LPS) is considered a hallmark of alcoholic liver disease (ALD). Intracellular mechanisms associated with LPS-induced signalling play a crucial role in the initiation and progression of alcoholic liver injury, and are being extensively explored. LPS recognition by Toll-like receptor 4 (TLR4) on macrophages and other cell types in the liver, activation of downstream signalling pathways culminating in activation of transcription factors such as NFκB, AP-1 leads to increased inflammatory cytokine production in ALD. In addition, LPS-induced MAPK such as ERK and p38 also contribute to liver injury. The importance of alcohol-induced reactive oxygen species and interactions with TLR pathways in macrophages leading to inflammation is becoming increasingly evident. Collectively, these signalling pathways induce pro- and anti-inflammatory cytokines that play an important role in ALD. In this review we describe the key signalling intermediates leading to alcohol-induced inflammation in alcoholic liver disease.
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DOI：
10.1002/hep.22470
发表时间：
2008-10
期刊：
Hepatology (Baltimore, Md.)
影响因子：
--
作者：
Hritz I;Mandrekar P;Velayudham A;Catalano D;Dolganiuc A;Kodys K;Kurt-Jones E;Szabo G
通讯作者：
Szabo G
DOI：
10.1152/ajpgi.00094.2004
发表时间：
2004-08-01
影响因子：
4.5
作者：
Hines, IN;Wheeler, MD
通讯作者：
Wheeler, MD
影响因子：
4.4
作者：
Ghosh, S
通讯作者：
Ghosh, S
DOI：
10.1111/j.1530-0277.2000.tb00012.x
发表时间：
2000-04-01
影响因子：
3.2
作者：
Fujimoto, M;Uemura, M;Fukui, H
通讯作者：
Fukui, H
DOI：
10.1016/s0006-291x(02)00586-7
发表时间：
2002-06-21
影响因子：
3.1
作者：
Cao, Q;Mak, KM;Lieber, CS
通讯作者：
Lieber, CS