Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
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
FullText
FullText_MUG
- Co-Autor*innen der Med Uni Graz
- Jost Philipp
- Altmetrics:
- Dimensions Citations:
- Plum Analytics:
- Scite (citation analytics):
- Abstract:
- 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