| First Author | Wuestefeld T | Year | 2005 |
| Journal | Hepatology | Volume | 42 |
| Issue | 5 | Pages | 1082-90 |
| PubMed ID | 16250046 | Mgi Jnum | J:191185 |
| Mgi Id | MGI:5461145 | Doi | 10.1002/hep.20912 |
| Citation | Wuestefeld T, et al. (2005) Lack of gp130 expression results in more bacterial infection and higher mortality during chronic cholestasis in mice. Hepatology 42(5):1082-90 |
| abstractText | 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. |
