Dissection of the intracellular pathways in hepatocytes suggests a role for Jun kinase and IFN regulatory factor-1 in Con A-induced liver failure.

K Streetz; B Fregien; J Plümpe; K Körber; S Kubicka; G Sass; S C Bischoff; M P Manns; Gisa Tiegs; C Trautwein

Dissection of the intracellular pathways in hepatocytes suggests a role for Jun kinase and IFN regulatory factor-1 in Con A-induced liver failure.

Standard

Dissection of the intracellular pathways in hepatocytes suggests a role for Jun kinase and IFN regulatory factor-1 in Con A-induced liver failure. / Streetz, K; Fregien, B; Plümpe, J; Körber, K; Kubicka, S; Sass, G; Bischoff, S C; Manns, M P; Tiegs, Gisa; Trautwein, C.

In: J IMMUNOL, Vol. 167, No. 1, 1, 2001, p. 514-523.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Streetz, K, Fregien, B, Plümpe, J, Körber, K, Kubicka, S, Sass, G, Bischoff, SC, Manns, MP, Tiegs, G & Trautwein, C 2001, 'Dissection of the intracellular pathways in hepatocytes suggests a role for Jun kinase and IFN regulatory factor-1 in Con A-induced liver failure.', J IMMUNOL, vol. 167, no. 1, 1, pp. 514-523. <http://www.ncbi.nlm.nih.gov/pubmed/11418690?dopt=Citation>

APA

Streetz, K., Fregien, B., Plümpe, J., Körber, K., Kubicka, S., Sass, G., Bischoff, S. C., Manns, M. P., Tiegs, G., & Trautwein, C. (2001). Dissection of the intracellular pathways in hepatocytes suggests a role for Jun kinase and IFN regulatory factor-1 in Con A-induced liver failure. J IMMUNOL, 167(1), 514-523. [1]. http://www.ncbi.nlm.nih.gov/pubmed/11418690?dopt=Citation

Vancouver

Streetz K, Fregien B, Plümpe J, Körber K, Kubicka S, Sass G et al. Dissection of the intracellular pathways in hepatocytes suggests a role for Jun kinase and IFN regulatory factor-1 in Con A-induced liver failure. J IMMUNOL. 2001;167(1):514-523. 1.

Bibtex

@article{830d0d66ea2849ad9d619c93266da6a8,

title = "Dissection of the intracellular pathways in hepatocytes suggests a role for Jun kinase and IFN regulatory factor-1 in Con A-induced liver failure.",

abstract = "Con A administration results in dose-dependent immune-mediated liver injury. Cytokines are important to determine the outcome of liver failure in this model, and especially TNF-alpha and IFN-gamma directly contribute to hepatocyte damage. The intracellular pathways of these two cytokines, which eventually result in tissue destruction, are not well defined. Here we used anti-IFN-gamma Abs and adenoviral vectors that express molecules inhibiting distinct TNF-alpha-dependent pathways in hepatocytes to better understand the relevance of specific intracellular signaling cascades for Con A-induced liver failure. We show that activation of TNF-alpha- and IFN-gamma-dependent intracellular pathways occurs prior to the influx of immune-activated cells into the liver and that anti-TNF-alpha and anti-IFN-gamma neutralizing Abs cannot block infiltration of these cells. Blocking experiments with Abs and adenoviral vectors showed that NF-kappaB activation and the Fas-associated death domain protein/caspase 8 cascade in hepatocytes during Con A-induced liver failure have no impact on tissue injury. Additionally, STAT1 activation alone after Con A injection in liver cells does not result in liver damage. In contrast, IFN-gamma-dependent expression of IFN regulatory factor-1 and TNF-alpha-dependent activation of c-Jun N-terminal kinase in liver cells correlates with liver cell damage after Con A injection. Therefore, our experiments indicate that 11418690",

keywords = "Animals, Humans, Male, Mice, Mice, Inbred BALB C, Tumor Cells, Cultured, NF-kappa B/metabolism, Injections, Intravenous, Cell Movement/immunology, Signal Transduction/immunology, *Adaptor Proteins, Signal Transducing, Antigens, CD45/biosynthesis, Antigens, CD95/metabolism, CD4-Positive T-Lymphocytes/pathology, Carrier Proteins/metabolism, Concanavalin A/*administration & dosage/pharmacology, DNA-Binding Proteins/antagonists & inhibitors/metabolism/*physiology, Fas-Associated Death Domain Protein, Hepatocytes/*enzymology/immunology/metabolism/pathology, Immune Sera/administration & dosage, Interferon Regulatory Factor-1, Interferon-gamma/antagonists & inhibitors/immunology/*physiology, Intracellular Fluid/*enzymology/immunology, JNK Mitogen-Activated Protein Kinases, Liver Failure/*enzymology/*immunology/pathology/prevention & control, Mitogen-Activated Protein Kinases/*physiology, Phosphoproteins/antagonists & inhibitors/metabolism/*physiology, STAT1 Transcription Factor, Trans-Activators/antagonists & inhibitors/metabolism, Tumor Necrosis Factor-alpha/pharmacology, Animals, Humans, Male, Mice, Mice, Inbred BALB C, Tumor Cells, Cultured, NF-kappa B/metabolism, Injections, Intravenous, Cell Movement/immunology, Signal Transduction/immunology, *Adaptor Proteins, Signal Transducing, Antigens, CD45/biosynthesis, Antigens, CD95/metabolism, CD4-Positive T-Lymphocytes/pathology, Carrier Proteins/metabolism, Concanavalin A/*administration & dosage/pharmacology, DNA-Binding Proteins/antagonists & inhibitors/metabolism/*physiology, Fas-Associated Death Domain Protein, Hepatocytes/*enzymology/immunology/metabolism/pathology, Immune Sera/administration & dosage, Interferon Regulatory Factor-1, Interferon-gamma/antagonists & inhibitors/immunology/*physiology, Intracellular Fluid/*enzymology/immunology, JNK Mitogen-Activated Protein Kinases, Liver Failure/*enzymology/*immunology/pathology/prevention & control, Mitogen-Activated Protein Kinases/*physiology, Phosphoproteins/antagonists & inhibitors/metabolism/*physiology, STAT1 Transcription Factor, Trans-Activators/antagonists & inhibitors/metabolism, Tumor Necrosis Factor-alpha/pharmacology",

author = "K Streetz and B Fregien and J Pl{\"u}mpe and K K{\"o}rber and S Kubicka and G Sass and Bischoff, {S C} and Manns, {M P} and Gisa Tiegs and C Trautwein",

year = "2001",

language = "English",

volume = "167",

pages = "514--523",

journal = "J IMMUNOL",

issn = "0022-1767",

publisher = "American Association of Immunologists",

number = "1",

}

RIS

TY - JOUR

T1 - Dissection of the intracellular pathways in hepatocytes suggests a role for Jun kinase and IFN regulatory factor-1 in Con A-induced liver failure.

AU - Streetz, K

AU - Fregien, B

AU - Plümpe, J

AU - Körber, K

AU - Kubicka, S

AU - Sass, G

AU - Bischoff, S C

AU - Manns, M P

AU - Tiegs, Gisa

AU - Trautwein, C

PY - 2001

Y1 - 2001

N2 - Con A administration results in dose-dependent immune-mediated liver injury. Cytokines are important to determine the outcome of liver failure in this model, and especially TNF-alpha and IFN-gamma directly contribute to hepatocyte damage. The intracellular pathways of these two cytokines, which eventually result in tissue destruction, are not well defined. Here we used anti-IFN-gamma Abs and adenoviral vectors that express molecules inhibiting distinct TNF-alpha-dependent pathways in hepatocytes to better understand the relevance of specific intracellular signaling cascades for Con A-induced liver failure. We show that activation of TNF-alpha- and IFN-gamma-dependent intracellular pathways occurs prior to the influx of immune-activated cells into the liver and that anti-TNF-alpha and anti-IFN-gamma neutralizing Abs cannot block infiltration of these cells. Blocking experiments with Abs and adenoviral vectors showed that NF-kappaB activation and the Fas-associated death domain protein/caspase 8 cascade in hepatocytes during Con A-induced liver failure have no impact on tissue injury. Additionally, STAT1 activation alone after Con A injection in liver cells does not result in liver damage. In contrast, IFN-gamma-dependent expression of IFN regulatory factor-1 and TNF-alpha-dependent activation of c-Jun N-terminal kinase in liver cells correlates with liver cell damage after Con A injection. Therefore, our experiments indicate that 11418690

AB - Con A administration results in dose-dependent immune-mediated liver injury. Cytokines are important to determine the outcome of liver failure in this model, and especially TNF-alpha and IFN-gamma directly contribute to hepatocyte damage. The intracellular pathways of these two cytokines, which eventually result in tissue destruction, are not well defined. Here we used anti-IFN-gamma Abs and adenoviral vectors that express molecules inhibiting distinct TNF-alpha-dependent pathways in hepatocytes to better understand the relevance of specific intracellular signaling cascades for Con A-induced liver failure. We show that activation of TNF-alpha- and IFN-gamma-dependent intracellular pathways occurs prior to the influx of immune-activated cells into the liver and that anti-TNF-alpha and anti-IFN-gamma neutralizing Abs cannot block infiltration of these cells. Blocking experiments with Abs and adenoviral vectors showed that NF-kappaB activation and the Fas-associated death domain protein/caspase 8 cascade in hepatocytes during Con A-induced liver failure have no impact on tissue injury. Additionally, STAT1 activation alone after Con A injection in liver cells does not result in liver damage. In contrast, IFN-gamma-dependent expression of IFN regulatory factor-1 and TNF-alpha-dependent activation of c-Jun N-terminal kinase in liver cells correlates with liver cell damage after Con A injection. Therefore, our experiments indicate that 11418690

KW - Animals

KW - Humans

KW - Male

KW - Mice

KW - Mice, Inbred BALB C

KW - Tumor Cells, Cultured

KW - NF-kappa B/metabolism

KW - Injections, Intravenous

KW - Cell Movement/immunology

KW - Signal Transduction/immunology

KW - Adaptor Proteins, Signal Transducing

KW - Antigens, CD45/biosynthesis

KW - Antigens, CD95/metabolism

KW - CD4-Positive T-Lymphocytes/pathology

KW - Carrier Proteins/metabolism

KW - Concanavalin A/administration & dosage/pharmacology

KW - DNA-Binding Proteins/antagonists & inhibitors/metabolism/physiology

KW - Fas-Associated Death Domain Protein

KW - Hepatocytes/enzymology/immunology/metabolism/pathology

KW - Immune Sera/administration & dosage

KW - Interferon Regulatory Factor-1

KW - Interferon-gamma/antagonists & inhibitors/immunology/physiology

KW - Intracellular Fluid/enzymology/immunology

KW - JNK Mitogen-Activated Protein Kinases

KW - Liver Failure/enzymology/immunology/pathology/prevention & control

KW - Mitogen-Activated Protein Kinases/physiology

KW - Phosphoproteins/antagonists & inhibitors/metabolism/physiology

KW - STAT1 Transcription Factor

KW - Trans-Activators/antagonists & inhibitors/metabolism

KW - Tumor Necrosis Factor-alpha/pharmacology