INTERLEUKIN 6 ROLE IN ALCOHOLIC LIVER CIRRHOSIS

白细胞介素 6 在酒精性肝硬化中的作用

• 批准号: 6731971
• 负责人: MARCOS ROJKIND
• 金额: $ 22.8万
• 依托单位: GEORGE WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-04-01 至 2006-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6731971
• 关键词: alcoholic liver cirrhosis; antifibrinolytic agents; biological signal transduction; colchicine; enzyme activity; fibrogenesis; gap junctions; gene expression; interleukin 6; laboratory mouse; liver cells; liver pharmacology; membrane channels; platelet derived growth factor; protein kinase; tissue /cell culture; tumor necrosis factor alpha

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.

描述：（根据研究者的摘要改编）：酒精引起的肝脏 肝硬化是全球死亡的主要原因，占50多个 由于肝硬化而导致的所有死亡的百分比。没有可靠的疗法 致命疾病，因此正在进行多次尝试 基于当前的新型抗纤维化剂 该疾病的病理生理学。本地事件和系统事件都起着关键作用 在肝肝硬化的发展中。在局部一级，具有纤维化和 通过肝星状细胞诱导I型胶原基因的表达。这些 细胞在控制门户血流中，产生多余的I型胶原蛋白 并收缩伤口。肝巨噬细胞和炎性细胞产生 细胞因子和生长因素在激活肝运动中起关键作用 星状细胞形成疤痕组织。在系统层面，一般响应 在非因素 - α和inteleukin-6的生物体中，它们是在此期间产生的 急性阶段，在启动肝星状细胞中起关键作用 扩散并制作I型胶原蛋白。调查员的长期目标是 定义分子机制，乙醇诱导肝纤维化和至 基于这些开发新颖和更合理的抗纤维化疗法 发现。在此应用程序中，他们建议实验以阐明基本 分子事件通常，急性期和肿瘤坏死 尤其是因子-Alpha和白介素-6，有助于纤维化 过程。因此，PI将在细胞和分子生物学中使用现代技术 解开参与肝激活涉及的信号转导途径 星状细胞并在建立急性相的途径中 细胞因子增强了乙醛的纤维化作用。而且， 研究人员将测试秋水仙碱是一种抗炎药 减轻活肝硬化的抗纤维化潜力对 要研究的参数。