Cytokines, including interleukins, growth factors, interferons and chemokines, are low-molecular-weight mediators of cellular communication produced by multiple cell types in the liver, including Kupffer cell, hepatic lymphocytes, endothelial cells, and stellate cells. The actions of cytokines are mediated through activation of several intracellular signaling pathways, including the Janus kinase-signal transducer and transcription factor (JAK-STAT), nuclear factor-kappa B, and mitogen-activated protein (MAP) kinases. A wide variety of cytokines are elevated in liver disease, however the roles of these cytokines in the liver remain obscure. The Section on Liver Biology is studying the role of cytokines and growth factors in alcoholic liver disease, viral hepatitis, and liver regeneration, and developing potential therapeutic approaches to treat these liver disorders. Our section has been focusing on two major cytokines and their signals in alcoholic liver disease and viral hepatitis: Interferon-gamma/STAT1; Interleukin-6/STAT3. In this year, we have demonstrated that (1) activation of innate immunity (NK/IFN-gamma) negatively regulates liver regeneration, (2) IL-6 treatment alleviates steatosis and ischemia/reperfusion injury in mice with fatty liver disease, (3) IL-22 plays a protective role in T cell hepatitis and IL-22 is a survival factor for hepatocytes via activation of STAT3, (3) IFN-gamma/STAT1 acts a pro-inflammatory signal in T cell-mediated hepatitis via induction of multiple chemokines and adhesion molecules via an IRF-dependent mechanism, (4) IL-6 prevents T cell-mediated hepatitis via inhibition of NKT cells.
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