Biological Significance and Therapeutic Potential of Cyt

细胞因子，包括白细胞介素、生长因子、干扰素和趋化因子，是肝脏中多种细胞类型（包括库普弗细胞、肝淋巴细胞、内皮细胞和星状细胞）产生的细胞通讯的低分子量介质。细胞因子的作用是通过激活多种细胞内信号通路介导的，包括Janus激酶信号转导和转录因子（JAK-STAT）、核因子κ B和丝裂原活化蛋白（MAP）激酶。多种细胞因子在肝脏疾病中升高，但这些细胞因子在肝脏中的作用仍不清楚。肝脏生物学部分正在研究细胞因子和生长因子在酒精性肝病、病毒性肝炎和肝脏再生中的作用，并开发治疗这些肝脏疾病的潜在治疗方法。本节主要关注酒精性肝病和病毒性肝炎中的两种主要细胞因子及其信号：干扰素- γ /STAT1；白细胞介素- 6 / STAT3。在这一年里，我们已经证明(1)先天免疫（NK/ ifn - γ）的激活负性调节肝脏再生，(2)IL-6治疗减轻脂肪变性和脂肪性肝脏疾病小鼠的缺血/再灌注损伤，(3)IL-22在T细胞肝炎中起保护作用，IL-22通过激活STAT3是肝细胞的生存因子。(3) ifn - γ /STAT1通过irf依赖机制诱导多种趋化因子和粘附分子，在T细胞介导的肝炎中发挥促炎信号作用；(4)IL-6通过抑制NKT细胞来预防T细胞介导的肝炎。

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.