INTERLEUKIN 6 ROLE IN ALCOHOLIC LIVER CIRRHOSIS

描述：（改编自研究者摘要）：酒精诱发的肝脏 肝硬化是全世界死亡的主要原因，占 50 多人的死亡原因 因肝硬化死亡的百分比。目前尚无有效的治疗方法 致命疾病，因此，正在多次尝试开发 基于现有知识的新型抗纤维化药物 该疾病的病理生理学。局部事件和系统事件都发挥着关键作用 在肝硬化的发展过程中。在局部水平上，是纤维化的并且 诱导肝星状细胞表达 I 型胶原蛋白基因。这些 细胞控制门脉血流，产生过量的 I 型胶原蛋白 并收缩伤口。肝脏巨噬细胞和炎症细胞产生 细胞因子和生长因子在激活肝脏中起关键作用 星状细胞形成疤痕组织。在系统层面，普遍反应 生物体转化为非因子-α和白细胞介素-6，它们是在 急性期，在启动肝星状细胞 增殖并产生 I 型胶原蛋白。研究者的长期目标是 定义乙醇诱导肝纤维化的分子机制并 在此基础上开发新颖且更合理的抗纤维化疗法 调查结果。在此应用中，他们提出了实验来解开基本原理 一般急性期和肿瘤坏死的分子事件 尤其是因子 α 和白细胞介素 6，有助于纤维化 过程。因此，PI 将使用细胞和分子生物学的现代技术 解开参与肝脏激活的信号转导途径 星状细胞并建立急性期的途径 细胞因子增强乙醛的纤维形成作用。此外， 研究人员将测试秋水仙碱（一种抗炎药）是否具有 改善活肝硬化的抗纤维化潜力对 待研究的参数。

DESCRIPTION: (Adapted from the Investigator's Abstract): Alcohol-induced liver cirrhosis is a leading cause of death worldwide and accounts for over 50 percent of all deaths due to cirrhosis. There is no proven therapy for this deadly disease and, therefore, multiple attempts are being made at developing novel anti-fibrogenic agents based on the current knowledge of the pathophysiology of the disease. Both local and systemic events play a key role in the development of liver cirrhosis. At a local level, are fibrogenic and induce the expression of type I collagen genes by hepatic stellate cells. These cells are in controlling portal blood flow, producing excess type I collagen and contracting the wound. Liver macrophages and inflammatory cells produce the cytokines and growth factors that play a key role in activating hepatic stellate cells to make scar tissue. At the systemic level, the general response of the organism to non-factor-alpha and inteleukin-6, which are produced during the acute phase, play a key role in priming hepatic stellate cells to proliferate and make type I collagen. The investigator's long-term goals are to define molecular mechanisms whereby ethanol induces liver fibrosis and to develop novel and more rational anti-fibrogenic therapies based on these findings. In this application they propose experiments to unravel basic molecular events whereby the acute phase in general, and tumor necrosis factor-alpha and interleukin-6 in particular, contribute to the fibrogenic process. Thus, the PI will use modern techniques in cell and molecular biology to unravel signal transduction pathways involved in the activation of hepatic stellate cells and in establishing pathways through which the acute phase cytokines enhance the fibrogenic actions of acetaldehyde. Moreover, the investigators will test whether colchicine, an anti-inflammatory drug with anti-fibrogenic potential that ameliorates live cirrhosis has an effect on the parameters to be investigated.