Kaufmann, Thomas; Jost, Philipp J; Pellegrini, Marc; Puthalakath, Hamsa; Gugasyan, Raffi; Gerondakis, Steve; Cretney, Erika; Smyth, Mark J; Silke, John; Hakem, Razq; Bouillet, Philippe; Mak, Tak W; Dixit, Vishva M; Strasser, Andreas (2009). Fatal hepatitis mediated by tumor necrosis factor TNFalpha requires caspase-8 and involves the BH3-only proteins Bid and Bim. Immunity, 30(1), pp. 56-66. Cambridge, Mass.: Cell Press 10.1016/j.immuni.2008.10.017
Full text not available from this repository. (Request a copy)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.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Pharmacology |
UniBE Contributor: |
Kaufmann, Thomas (B) |
ISSN: |
1074-7613 |
Publisher: |
Cell Press |
Language: |
English |
Submitter: |
Factscience Import |
Date Deposited: |
04 Oct 2013 15:10 |
Last Modified: |
29 Mar 2023 23:33 |
Publisher DOI: |
10.1016/j.immuni.2008.10.017 |
PubMed ID: |
19119023 |
Web of Science ID: |
000262769900010 |
URI: |
https://boris.unibe.ch/id/eprint/30682 (FactScience: 194947) |
Actions (login required)
 |
Edit item |