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Tumor necrosis factor-induced hepatocyte apoptosis precedes liver failure in experimental murine shock models

Tumor necrosis factor-induced hepatocyte apoptosis precedes liver failure in experimental murine shock models

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LEIST, Marcel, Florian GANTNER, Ines BOHLINGER, Gisa TIEGS, Paul Georg GERMANN, Albrecht WENDEL, 1995. Tumor necrosis factor-induced hepatocyte apoptosis precedes liver failure in experimental murine shock models. In: American Journal of Pathology. 146(5), pp. 1220-1234

@article{Leist1995Tumor-7828, title={Tumor necrosis factor-induced hepatocyte apoptosis precedes liver failure in experimental murine shock models}, year={1995}, number={5}, volume={146}, journal={American Journal of Pathology}, pages={1220--1234}, author={Leist, Marcel and Gantner, Florian and Bohlinger, Ines and Tiegs, Gisa and Germann, Paul Georg and Wendel, Albrecht} }

<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:bibo="http://purl.org/ontology/bibo/" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:xsd="http://www.w3.org/2001/XMLSchema#" > <rdf:Description rdf:about="https://kops.uni-konstanz.de/rdf/resource/123456789/7828"> <dc:creator>Gantner, Florian</dc:creator> <dc:date rdf:datatype="http://www.w3.org/2001/XMLSchema#dateTime">2011-03-24T17:37:50Z</dc:date> <dc:creator>Wendel, Albrecht</dc:creator> <dc:creator>Leist, Marcel</dc:creator> <dcterms:issued>1995</dcterms:issued> <dc:creator>Germann, Paul Georg</dc:creator> <dc:contributor>Leist, Marcel</dc:contributor> <dc:creator>Bohlinger, Ines</dc:creator> <dcterms:rights rdf:resource="http://nbn-resolving.org/urn:nbn:de:bsz:352-20140905103416863-3868037-7"/> <dc:language>eng</dc:language> <dc:contributor>Tiegs, Gisa</dc:contributor> <dc:rights>deposit-license</dc:rights> <dcterms:abstract xml:lang="eng">We investigated the role of hepatocyte apoptosis in four different murine models of acute inflammatory liver failure. Liver damage induced in D-galactosamine-sensitized mice by endotoxin infection was initiated by processes typical of apoptosis, ie, chromatin condensation, DNA fragmentation, and formation of intracellular apoptotic bodies. DNA was cleaved into oligonucleosomal fragments in the liver before a significant rise of alanine aminotransferase in plasma occurred. Passive immunization against tumor necrosis factor (TNF) completely inhibited the injury caused by endotoxin. Direct injection of recombinant TNF-alpha also caused DNA fragmentation followed by alanine aminotransferase release into the plasma. Pretreatment of mice with interleukin-1 beta, which is known to suppress TNF-induced lethality, completely prevented apoptosis and liver failure in this model. These results demonstrate the causal role of TNF in endotoxin-induced hepatic apoptosis. TNF-inducible hepatocyte apoptosis in vivo was not only observed in D-galactosamine-sensitized mice, but also when the alternative transcriptional inhibitor actinomycin D was used. In mice injected with the TNF-inducing T cell mitogen concanavalin A, hepatic apoptosis was even noticed without requirement of additional sensitizers. We conclude that TNF-induced hepatocyte apoptosis is an early, general, and possibly causal event during experimental liver failure triggered by inflammatory stimuli.</dcterms:abstract> <dc:contributor>Wendel, Albrecht</dc:contributor> <dcterms:bibliographicCitation>First publ. in: American Journal of Pathology ; 146 (1995), 5. - S. 1220-1234</dcterms:bibliographicCitation> <dcterms:title>Tumor necrosis factor-induced hepatocyte apoptosis precedes liver failure in experimental murine shock models</dcterms:title> <bibo:uri rdf:resource="http://kops.uni-konstanz.de/handle/123456789/7828"/> <dc:creator>Tiegs, Gisa</dc:creator> <dc:contributor>Germann, Paul Georg</dc:contributor> <dc:format>application/pdf</dc:format> <dc:contributor>Bohlinger, Ines</dc:contributor> <dc:contributor>Gantner, Florian</dc:contributor> </rdf:Description> </rdf:RDF>

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