Wuestefeld, T. and Klein, C. and Streetz, K. L. and Beraza, N. and Schoelmerich, Juergen and Burgart, L. and Zender, L. and Kubicka, S. and Gores, G J. and Manns, M P. and Trautwein, Christian (2005) Lack of gp130 expression results in more bacterial infection and higher mortality during chronic cholestasis in mice. HEPATOLOGY, 42 (5). pp. 1082-1090. ISSN 0270-9139, 1527-3350
Full text not available from this repository. (Request a copy)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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | LIVER-INJURY; INTERLEUKIN-6-DEFICIENT MICE; DUCTULAR REACTION; ENDOTOXIN; HEPATOCYTES; CELLS; STAT3; COMPENSATION; REGENERATION; MECHANISMS; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin I |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 23 Apr 2021 10:41 |
| Last Modified: | 23 Apr 2021 10:41 |
| URI: | https://pred.uni-regensburg.de/id/eprint/35469 |
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