胆汁淤积
肝病学
糖蛋白130
内科学
败血症
医学
免疫学
内分泌学
生物
炎症
白细胞介素6
作者
Torsten Wüestefeld,Christian Klein,Konrad L. Streetz,Naiara Beraza,Jürgen Schölmerich,Lawrence J. Burgart,Lars Zender,Stefan Kubicka,Gregory J. Gores,Michael P. Manns,Christian Trautwein
出处
期刊:Hepatology
[Lippincott Williams & Wilkins]
日期:2005-10-26
卷期号:42 (5): 1082-1090
被引量:33
摘要
Abstract Chronic cholestasis is associated with increased bacterial infections and sepsis resulting in higher mortality in humans. In the current study, we investigated the relevance of gp130-dependent pathways after bile duct ligation (BDL). BDL was performed in conditional gp130 knockout (loxP/Cre system) mice and respective controls. Liver injury, regulation of the acute phase response, and the impact on survival and bacterial infections were determined. Acute BDL resulted in increased IL-6 levels, Stat3 activation, and an increase in acute-phase proteins (serum-amyloid-A [SAA]), which was blocked in gp130-deleted animals. In addition, the antimicrobial gene hepcidin was regulated in a gp130-dependent manner after BDL. During chronic cholestasis Stat3 activation was dramatically reduced, while high SAA levels were maintained via gp130-dependent signaling. Inhibition of gp130-dependent pathways resulted in higher mortality and liver damage, which was associated with higher infiltration of immune-activated cells and increased germ number in the liver. In conclusion , during acute and chronic cholestasis, the gp130 system is essential for controlling the acute-phase response. Lack of gp130 expression results in pronounced bacterial growth in bile and liver after BDL, which is associated with higher mortality. Activation of gp130-dependent pathways after BDL is essential and appears to be a therapeutic target during cholestasis. (Hepatology 2005;42:1082–1090.)
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