Lack of gp130 expression results in more bacterial infection and higher mortality during chronic cholestasis in mice

Torsten Wuestefeld, Christian Klein, Konrad L. Streetz, Naiara Beraza, Jürgen Schölmerich, Lawrence J. Burgart, Lars Zender, Stefan Kubicka, Gregory James Gores, Michael P. Manns, Christian Trautwein

Research output: Contribution to journalArticle

24 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1082-1090
Number of pages9
JournalHepatology
Volume42
Issue number5
DOIs
StatePublished - Nov 2005

Fingerprint

Cholestasis
Bile Ducts
Bacterial Infections
Ligation
Mortality
Serum Amyloid A Protein
Acute-Phase Reaction
Liver
Hepcidins
Acute-Phase Proteins
Germ Cells
Bile
Interleukin-6
Sepsis
Survival
Wounds and Injuries
Growth
Genes

ASJC Scopus subject areas

  • Hepatology

Cite this

Wuestefeld, T., Klein, C., Streetz, K. L., Beraza, N., Schölmerich, J., Burgart, L. J., ... Trautwein, C. (2005). Lack of gp130 expression results in more bacterial infection and higher mortality during chronic cholestasis in mice. Hepatology, 42(5), 1082-1090. https://doi.org/10.1002/hep.20912

Lack of gp130 expression results in more bacterial infection and higher mortality during chronic cholestasis in mice. / Wuestefeld, Torsten; Klein, Christian; Streetz, Konrad L.; Beraza, Naiara; Schölmerich, Jürgen; Burgart, Lawrence J.; Zender, Lars; Kubicka, Stefan; Gores, Gregory James; Manns, Michael P.; Trautwein, Christian.

In: Hepatology, Vol. 42, No. 5, 11.2005, p. 1082-1090.

Research output: Contribution to journalArticle

Wuestefeld, T, Klein, C, Streetz, KL, Beraza, N, Schölmerich, J, Burgart, LJ, Zender, L, Kubicka, S, Gores, GJ, Manns, MP & Trautwein, C 2005, 'Lack of gp130 expression results in more bacterial infection and higher mortality during chronic cholestasis in mice', Hepatology, vol. 42, no. 5, pp. 1082-1090. https://doi.org/10.1002/hep.20912
Wuestefeld T, Klein C, Streetz KL, Beraza N, Schölmerich J, Burgart LJ et al. Lack of gp130 expression results in more bacterial infection and higher mortality during chronic cholestasis in mice. Hepatology. 2005 Nov;42(5):1082-1090. https://doi.org/10.1002/hep.20912
Wuestefeld, Torsten ; Klein, Christian ; Streetz, Konrad L. ; Beraza, Naiara ; Schölmerich, Jürgen ; Burgart, Lawrence J. ; Zender, Lars ; Kubicka, Stefan ; Gores, Gregory James ; Manns, Michael P. ; Trautwein, Christian. / Lack of gp130 expression results in more bacterial infection and higher mortality during chronic cholestasis in mice. In: Hepatology. 2005 ; Vol. 42, No. 5. pp. 1082-1090.
@article{5435fce9238340ffac9bc0ed492c4361,
title = "Lack of gp130 expression results in more bacterial infection and higher mortality during chronic cholestasis in mice",
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.",
author = "Torsten Wuestefeld and Christian Klein and Streetz, {Konrad L.} and Naiara Beraza and J{\"u}rgen Sch{\"o}lmerich and Burgart, {Lawrence J.} and Lars Zender and Stefan Kubicka and Gores, {Gregory James} and Manns, {Michael P.} and Christian Trautwein",
year = "2005",
month = "11",
doi = "10.1002/hep.20912",
language = "English (US)",
volume = "42",
pages = "1082--1090",
journal = "Hepatology",
issn = "0270-9139",
publisher = "John Wiley and Sons Ltd",
number = "5",

}

TY - JOUR

T1 - Lack of gp130 expression results in more bacterial infection and higher mortality during chronic cholestasis in mice

AU - Wuestefeld, Torsten

AU - Klein, Christian

AU - Streetz, Konrad L.

AU - Beraza, Naiara

AU - Schölmerich, Jürgen

AU - Burgart, Lawrence J.

AU - Zender, Lars

AU - Kubicka, Stefan

AU - Gores, Gregory James

AU - Manns, Michael P.

AU - Trautwein, Christian

PY - 2005/11

Y1 - 2005/11

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=30944469496&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=30944469496&partnerID=8YFLogxK

U2 - 10.1002/hep.20912

DO - 10.1002/hep.20912

M3 - Article

C2 - 16250046

AN - SCOPUS:30944469496

VL - 42

SP - 1082

EP - 1090

JO - Hepatology

JF - Hepatology

SN - 0270-9139

IS - 5

ER -