Intracellular survival pathways in the liver.
Recent studies have drawn attention to cytokines as important modulators of hepatocyte cell death during acute and chronic liver disease. Through interaction with cell surface receptors, they activate specific intracellular pathways that influence cell fate in different manners. For example, tumor necrosis factor not only induces proapoptotic signals via the caspase cascade but also activates intracellular survival pathways, namely the nuclear factor (NF)-kappaB pathway. In this article, we will focus on the function of the NF-kappaB pathway in liver physiology and pathology. Especially, recent data based on experiments with genetically modified mice will be discussed, which demonstrated important and controversial functions of this pathway e.g. in cytokine-mediated hepatocyte apoptosis, ischemia-reperfusion injury, liver regeneration and the development of hepatocellular carcinoma. Moreover, the role of the interleukin-6 pathway and its possible protective function in the context of liver failure will be summarized.
Luedde
Tom
T
EMBL Mouse Biology Program, Monterotondo, Italy.
Trautwein
Christian
C
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D006528:Carcinoma, Hepatocellular / Q000209:etiology; D022781:Hepatocytes / Q000166:cytology; D006801:Humans; D051550:I-kappa B Kinase / Q000502:physiology; D015850:Interleukin-6 / Q000502:physiology; D008099:Liver / Q000098:blood supply / Q000166:cytology*; D008113:Liver Neoplasms / Q000209:etiology; D016328:NF-kappa B / Q000502:physiology*; D015427:Reperfusion Injury / Q000209:etiology; D015398:Signal Transduction / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology
D015850:Interleukin-6; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; C496559:CHUK protein, human; D051550:I-kappa B Kinase