Mechanisms of liver disease: cross-talk between the NF-κB and JNK pathways
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Salvatore Papa
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)α and interleukin-6 (IL-6) are key mediators of these processes and activate different cellular response such as proliferation, survival and death. TNFα 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-κB promotes survival, c-Jun N-terminal kinases (JNKs) and caspases are strategic effectors of cell death in the TNFα-mediated signaling pathway. This review summarizes recent advances in the mechanisms of TNFα-induced hepatotoxicity and suggests that NF-κB plays a protective role against JNK-induced hepatocyte death. Identification of the mechanisms regulating interplay between the NF-κB and JNK pathways is required in the search for novel targets for the treatment of liver disease, including hepatitis and hepatocellular carcinoma.
©2009 by Walter de Gruyter Berlin New York
Articles in the same Issue
- Guest Editorial
- Highlight: ‘Regenerative Hepatology’
- Highlight: Regenerative Hepatology
- The do's and don'ts of p53 isoforms
- Mechanisms of liver disease: cross-talk between the NF-κB and JNK pathways
- Immunologic hurdles of therapeutic stem cell transplantation
- Ancestral vascular tube formation and its adoption by tumors
- Cellular plasticity of the pancreas
- Hepatic and pancreatic stellate cells in focus
- Interplay between host cell and hepatitis C virus in regulating viral replication
- Epidermal growth factor receptor signaling in liver cell proliferation and apoptosis
- The chemokine scavenging receptor D6 limits acute toxic liver injury in vivo
- Hepatic differentiation of pluripotent stem cells
- Protein Structure and Function
- Effect of curcumin on amyloidogenic property of molten globule-like intermediate state of 2,5-diketo-d-gluconate reductase A
- Cell Biology and Signaling
- Specific induction of migration and invasion of pancreatic carcinoma cells by RhoC, which differs from RhoA in its localisation and activity
- Autoregulatory control of the p53 response by Siah-1L-mediated HIPK2 degradation
Articles in the same Issue
- Guest Editorial
- Highlight: ‘Regenerative Hepatology’
- Highlight: Regenerative Hepatology
- The do's and don'ts of p53 isoforms
- Mechanisms of liver disease: cross-talk between the NF-κB and JNK pathways
- Immunologic hurdles of therapeutic stem cell transplantation
- Ancestral vascular tube formation and its adoption by tumors
- Cellular plasticity of the pancreas
- Hepatic and pancreatic stellate cells in focus
- Interplay between host cell and hepatitis C virus in regulating viral replication
- Epidermal growth factor receptor signaling in liver cell proliferation and apoptosis
- The chemokine scavenging receptor D6 limits acute toxic liver injury in vivo
- Hepatic differentiation of pluripotent stem cells
- Protein Structure and Function
- Effect of curcumin on amyloidogenic property of molten globule-like intermediate state of 2,5-diketo-d-gluconate reductase A
- Cell Biology and Signaling
- Specific induction of migration and invasion of pancreatic carcinoma cells by RhoC, which differs from RhoA in its localisation and activity
- Autoregulatory control of the p53 response by Siah-1L-mediated HIPK2 degradation
