Format

Send to

Choose Destination
See comment in PubMed Commons below
Biol Chem. 2009 Oct;390(10):965-76. doi: 10.1515/BC.2009.111.

Mechanisms of liver disease: cross-talk between the NF-kappaB and JNK pathways.

Author information

1
Department of Immunology, Investigative Science, Imperial College London, London W12 0NN, UK. s.papa@imperial.ac.uk

Abstract

The liver plays a central role in the transformation and degradation of endogenous and exogenous chemicals, and in the removal of unwanted cells such as damaged, genetically mutated and virus-infected cells. Because of this function, the liver is susceptible to toxicity caused by the products generated during these natural occurrences. Hepatocyte death is the major feature of liver injury. In response to liver injury, specific intracellular processes are initiated to maintain liver integrity. Inflammatory cytokines including tumor necrosis factor (TNF)alpha and interleukin-6 (IL-6) are key mediators of these processes and activate different cellular response such as proliferation, survival and death. TNFalpha induces specific signaling pathways in hepatocytes that lead to activation of either pro-survival mediators or effectors of cell death. Whereas activation of transcription factor NF-kappaB promotes survival, c-Jun N-terminal kinases (JNKs) and caspases are strategic effectors of cell death in the TNFalpha-mediated signaling pathway. This review summarizes recent advances in the mechanisms of TNFalpha-induced hepatotoxicity and suggests that NF-kappaB plays a protective role against JNK-induced hepatocyte death. Identification of the mechanisms regulating interplay between the NF-kappaB and JNK pathways is required in the search for novel targets for the treatment of liver disease, including hepatitis and hepatocellular carcinoma.

PMID:
19642868
PMCID:
PMC2775491
DOI:
10.1515/BC.2009.111
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for iFactory Icon for PubMed Central
    Loading ...
    Support Center