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Kupffer cell-expressed membrane-bound TNF mediates melphalan hepatotoxicity via activation of both TNF receptors.

Standard

Kupffer cell-expressed membrane-bound TNF mediates melphalan hepatotoxicity via activation of both TNF receptors. / Kresse, Matthias; Latta, Markus; Künstle, Gerald; Riehle, Hans-Martin; van Rooijen, Nico; Hentze, Hannes; Tiegs, Gisa; Biburger, Markus; Lucas, Rudolf; Wendel, Albrecht.

in: J IMMUNOL, Jahrgang 175, Nr. 6, 6, 2005, S. 4076-4083.

Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung

Harvard

Kresse, M, Latta, M, Künstle, G, Riehle, H-M, van Rooijen, N, Hentze, H, Tiegs, G, Biburger, M, Lucas, R & Wendel, A 2005, 'Kupffer cell-expressed membrane-bound TNF mediates melphalan hepatotoxicity via activation of both TNF receptors.', J IMMUNOL, Jg. 175, Nr. 6, 6, S. 4076-4083. <http://www.ncbi.nlm.nih.gov/pubmed/16148157?dopt=Citation>

APA

Kresse, M., Latta, M., Künstle, G., Riehle, H-M., van Rooijen, N., Hentze, H., Tiegs, G., Biburger, M., Lucas, R., & Wendel, A. (2005). Kupffer cell-expressed membrane-bound TNF mediates melphalan hepatotoxicity via activation of both TNF receptors. J IMMUNOL, 175(6), 4076-4083. [6]. http://www.ncbi.nlm.nih.gov/pubmed/16148157?dopt=Citation

Vancouver

Kresse M, Latta M, Künstle G, Riehle H-M, van Rooijen N, Hentze H et al. Kupffer cell-expressed membrane-bound TNF mediates melphalan hepatotoxicity via activation of both TNF receptors. J IMMUNOL. 2005;175(6):4076-4083. 6.

Bibtex

@article{88d0a44f4df1472abc8160f98077cfdf,
title = "Kupffer cell-expressed membrane-bound TNF mediates melphalan hepatotoxicity via activation of both TNF receptors.",
abstract = "Isolated hepatic perfusion of nonresectable liver cancer using the combination of TNF and melphalan can be associated with a treatment-related hepatotoxicity. We investigated whether, apart from TNF, also melphalan is cytotoxic in primary murine liver cells in vitro and investigated mediators, mode of cell death, and cell types involved. Melphalan induced a caspase-dependent apoptosis in hepatocytes, which was not seen in liver cell preparations depleted of Kupffer cells. Neutralization of TNF prevented melphalan-induced apoptosis and liver cells derived from mice genetically deficient in either TNFR 1 or 2, but not from lpr mice lacking a functional CD95 receptor, were completely resistant. Cell-cell contact between hepatocytes and Kupffer cells was required for apoptosis to occur. Melphalan increased membrane-bound but not secreted TNF in Kupffer cells and inhibited recombinant TNF-alpha converting enzyme in vitro. Melphalan induced also severe hepatotoxicity in the isolated recirculating perfused mouse liver from wild-type mice but not from TNFR 1 or 2 knockout mice. In conclusion, this study shows that melphalan elicits membrane TNF on Kupffer cells due to inhibition of TNF processing and thereby initiates apoptosis of hepatocytes via obligatory activation of both TNFRs. The identification of this novel mechanism allows a causal understanding of melphalan-induced hepatotoxicity.",
keywords = "Animals, Male, Cells, Cultured, Mice, Mice, Inbred C57BL, Mice, Knockout, Apoptosis, Cell Communication, Caspases/metabolism, ADAM Proteins/antagonists & inhibitors, *Drug-Induced Liver Injury, Hepatocytes/pathology, Kupffer Cells/*metabolism, Liver Diseases/etiology, Melphalan/*adverse effects, Membrane Proteins, Receptors, Tumor Necrosis Factor, Type I/*metabolism, Receptors, Tumor Necrosis Factor, Type II/*metabolism, Tumor Necrosis Factor-alpha/*metabolism, Animals, Male, Cells, Cultured, Mice, Mice, Inbred C57BL, Mice, Knockout, Apoptosis, Cell Communication, Caspases/metabolism, ADAM Proteins/antagonists & inhibitors, *Drug-Induced Liver Injury, Hepatocytes/pathology, Kupffer Cells/*metabolism, Liver Diseases/etiology, Melphalan/*adverse effects, Membrane Proteins, Receptors, Tumor Necrosis Factor, Type I/*metabolism, Receptors, Tumor Necrosis Factor, Type II/*metabolism, Tumor Necrosis Factor-alpha/*metabolism",
author = "Matthias Kresse and Markus Latta and Gerald K{\"u}nstle and Hans-Martin Riehle and {van Rooijen}, Nico and Hannes Hentze and Gisa Tiegs and Markus Biburger and Rudolf Lucas and Albrecht Wendel",
year = "2005",
language = "English",
volume = "175",
pages = "4076--4083",
journal = "J IMMUNOL",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "6",

}

RIS

TY - JOUR

T1 - Kupffer cell-expressed membrane-bound TNF mediates melphalan hepatotoxicity via activation of both TNF receptors.

AU - Kresse, Matthias

AU - Latta, Markus

AU - Künstle, Gerald

AU - Riehle, Hans-Martin

AU - van Rooijen, Nico

AU - Hentze, Hannes

AU - Tiegs, Gisa

AU - Biburger, Markus

AU - Lucas, Rudolf

AU - Wendel, Albrecht

PY - 2005

Y1 - 2005

N2 - Isolated hepatic perfusion of nonresectable liver cancer using the combination of TNF and melphalan can be associated with a treatment-related hepatotoxicity. We investigated whether, apart from TNF, also melphalan is cytotoxic in primary murine liver cells in vitro and investigated mediators, mode of cell death, and cell types involved. Melphalan induced a caspase-dependent apoptosis in hepatocytes, which was not seen in liver cell preparations depleted of Kupffer cells. Neutralization of TNF prevented melphalan-induced apoptosis and liver cells derived from mice genetically deficient in either TNFR 1 or 2, but not from lpr mice lacking a functional CD95 receptor, were completely resistant. Cell-cell contact between hepatocytes and Kupffer cells was required for apoptosis to occur. Melphalan increased membrane-bound but not secreted TNF in Kupffer cells and inhibited recombinant TNF-alpha converting enzyme in vitro. Melphalan induced also severe hepatotoxicity in the isolated recirculating perfused mouse liver from wild-type mice but not from TNFR 1 or 2 knockout mice. In conclusion, this study shows that melphalan elicits membrane TNF on Kupffer cells due to inhibition of TNF processing and thereby initiates apoptosis of hepatocytes via obligatory activation of both TNFRs. The identification of this novel mechanism allows a causal understanding of melphalan-induced hepatotoxicity.

AB - Isolated hepatic perfusion of nonresectable liver cancer using the combination of TNF and melphalan can be associated with a treatment-related hepatotoxicity. We investigated whether, apart from TNF, also melphalan is cytotoxic in primary murine liver cells in vitro and investigated mediators, mode of cell death, and cell types involved. Melphalan induced a caspase-dependent apoptosis in hepatocytes, which was not seen in liver cell preparations depleted of Kupffer cells. Neutralization of TNF prevented melphalan-induced apoptosis and liver cells derived from mice genetically deficient in either TNFR 1 or 2, but not from lpr mice lacking a functional CD95 receptor, were completely resistant. Cell-cell contact between hepatocytes and Kupffer cells was required for apoptosis to occur. Melphalan increased membrane-bound but not secreted TNF in Kupffer cells and inhibited recombinant TNF-alpha converting enzyme in vitro. Melphalan induced also severe hepatotoxicity in the isolated recirculating perfused mouse liver from wild-type mice but not from TNFR 1 or 2 knockout mice. In conclusion, this study shows that melphalan elicits membrane TNF on Kupffer cells due to inhibition of TNF processing and thereby initiates apoptosis of hepatocytes via obligatory activation of both TNFRs. The identification of this novel mechanism allows a causal understanding of melphalan-induced hepatotoxicity.

KW - Animals

KW - Male

KW - Cells, Cultured

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Knockout

KW - Apoptosis

KW - Cell Communication

KW - Caspases/metabolism

KW - ADAM Proteins/antagonists & inhibitors

KW - Drug-Induced Liver Injury

KW - Hepatocytes/pathology

KW - Kupffer Cells/metabolism

KW - Liver Diseases/etiology

KW - Melphalan/adverse effects

KW - Membrane Proteins

KW - Receptors, Tumor Necrosis Factor, Type I/metabolism

KW - Receptors, Tumor Necrosis Factor, Type II/metabolism

KW - Tumor Necrosis Factor-alpha/metabolism

KW - Animals

KW - Male

KW - Cells, Cultured

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Knockout

KW - Apoptosis

KW - Cell Communication

KW - Caspases/metabolism

KW - ADAM Proteins/antagonists & inhibitors

KW - Drug-Induced Liver Injury

KW - Hepatocytes/pathology

KW - Kupffer Cells/metabolism

KW - Liver Diseases/etiology

KW - Melphalan/adverse effects

KW - Membrane Proteins

KW - Receptors, Tumor Necrosis Factor, Type I/metabolism

KW - Receptors, Tumor Necrosis Factor, Type II/metabolism

KW - Tumor Necrosis Factor-alpha/metabolism

M3 - SCORING: Journal article

VL - 175

SP - 4076

EP - 4083

JO - J IMMUNOL

JF - J IMMUNOL

SN - 0022-1767

IS - 6

M1 - 6

ER -