Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz

Logo MUG-Forschungsportal

Gewählte Publikation:

SHR Neuro Krebs Kardio Lipid Stoffw Microb

Kaufmann, T; Jost, PJ; Pellegrini, M; Puthalakath, H; Gugasyan, R; Gerondakis, S; Cretney, E; Smyth, MJ; Silke, J; Hakem, R; Bouillet, P; Mak, TW; Dixit, VM; Strasser, A.
Fatal hepatitis mediated by tumor necrosis factor TNFalpha requires caspase-8 and involves the BH3-only proteins Bid and Bim.
Immunity. 2009; 30(1):56-66 Doi: 10.1016/j.immuni.2008.10.017 [OPEN ACCESS]
Web of Science PubMed PUBMED Central FullText FullText_MUG


Co-Autor*innen der Med Uni Graz
Jost Philipp

Dimensions Citations:

Plum Analytics:

Scite (citation analytics):

Apoptotic death of hepatocytes, a contributor to many chronic and acute liver diseases, can be a consequence of overactivation of the immune system and is often mediated by TNFalpha. Injection with lipopolysaccharide (LPS) plus the transcriptional inhibitor D(+)-galactosamine (GalN) or mitogenic T cell activation causes fatal hepatocyte apoptosis in mice, which is mediated by TNFalpha, but the effector mechanisms remain unclear. Our analysis of gene-targeted mice showed that caspase-8 is essential for hepatocyte killing in both settings. Loss of Bid, the proapoptotic BH3-only protein activated by caspase-8 and essential for Fas ligand-induced hepatocyte killing, resulted only in a minor reduction of liver damage. However, combined loss of Bid and another BH3-only protein, Bim, activated by c-Jun N-terminal kinase (JNK), protected mice from LPS+GalN-induced hepatitis. These observations identify caspase-8 and the BH3-only proteins Bid and Bim as potential therapeutic targets for treatment of inflammatory liver diseases.
Find related publications in this database (using NLM MeSH Indexing)
Animals -
Apoptosis -
Apoptosis Regulatory Proteins - metabolism
BH3 Interacting Domain Death Agonist Protein - metabolism
Bcl-2-Like Protein 11 -
Caspase 8 - metabolism
Chemical and Drug Induced Liver Injury -
Hepatocytes - pathology
Membrane Proteins - metabolism
Mice -
Mice, Inbred C57BL -
Mice, Knockout -
Proto-Oncogene Proteins - metabolism
Tumor Necrosis Factor-alpha - metabolism
Tumor Necrosis Factor-alpha - pharmacology

© Med Uni Graz Impressum