The role of inflammation in cholestasis: clinical and basic aspects.
The role of inflammation in cholestasis: clinical and basic aspects.
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DOI：
10.1055/s-0030-1253227
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发表时间：
2010-05
影响因子：
4.2
通讯作者：
Karpen SJ
中科院分区：
文献类型：
--
作者：
Kosters A;Karpen SJ
肝胆转运系统对包括胆汁酸在内的各种化合物的摄取和排泄是必不可少的。这种排泄途径的破坏和失调会导致胆汁淤积，导致胆汁酸和其他有毒化合物在肝脏内积聚，并伴随着肝脏病理的进展。炎症引起的胆汁淤积是肝外感染或炎性过程患者的常见并发症，通常被称为脓毒症相关性胆汁淤积。微生物产品，包括内毒素，直接或通过激活促炎细胞因子在肝细胞内诱导信号通路，导致胆汁流量迅速和显著减少。炎症信号会抑制关键的肝胆转运蛋白的表达和功能。这些促炎信号级联反应导致大量核转录调节因子的表达和活性受到抑制，其中许多调节因子对维持肝胆转运蛋白基因的表达是必不可少的。有趣的是，最近发现的胆汁酸激活的核受体和促炎性核介质之间的分子串扰可能为理解肝脏内的适应过程提供了新的手段。总之，炎症诱导的胆汁淤积以及胆汁淤积中滞留分子对炎症信号的影响在肝脏中交织在一起，为研究和治疗提供了潜在的机会。
Hepatobiliary transport systems are essential for the uptake and excretion of a variety of compounds including bile acids. Disruption and dysregulation of this excretory pathway results in cholestasis, leading to the intrahepatic accumulation of bile acids and other toxic compounds with progression of liver pathology. Cholestasis induced by inflammation is a common complication in patients with extrahepatic infections or inflammatory processes, generally referred to as sepsis-associated cholestasis. Microbial products, including endotoxin, induce signaling pathways within hepatocytes either directly, or through activation of pro-inflammatory cytokines, leading to rapid and profound reductions in bile flow. The expression and function of key hepatobiliary transporters are suppressed in response to inflammatory signaling. These pro-inflammatory signaling cascades lead to repressed expression and activity of a large number of nuclear transcriptional regulators, many of which are essential for maintenance of hepatobiliary transporter gene expression. Interestingly, recently discovered molecular crosstalk between bile acid activated nuclear receptors and pro-inflammatory nuclear mediators may provide new means of understanding adaptive processes within liver. All together, inflammation-induced cholestasis, and the effects of retained molecules in cholestasis on inflammatory signals, are interwoven in the liver, providing potential opportunities for research and therapeutics.
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影响因子：
13.5
作者：
Geier, A;Zollner, G;Trauner, M
通讯作者：
Trauner, M
DOI：
10.1152/ajpgi.00539.2005
发表时间：
2006-06-01
影响因子：
4.5
作者：
Boyer, James L.;Trauner, Michael;Ballatori, Nazzareno
通讯作者：
Ballatori, Nazzareno
影响因子：
13.5
作者：
Geier, A;Dietrich, CG;Gartung, C
通讯作者：
Gartung, C
影响因子：
3.7
作者：
Donner, MG;Warskulat, U;Häussinger, D
通讯作者：
Häussinger, D
影响因子：
2
作者：
Brcakova, Eva;Fuksa, Leos;Micuda, Stanislav
通讯作者：
Micuda, Stanislav