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：（改编自研究者摘要）：酒精诱导的肝脏 肝硬化是全世界死亡的主要原因， %的人死于肝硬化。目前还没有有效的治疗方法 致命的疾病，因此，正在进行多种尝试， 新的抗纤维化剂的基础上，目前的知识， 疾病的病理生理学。局部和系统性事件都起着关键作用 在肝硬化的发展过程中。在局部水平上，是纤维化的， 诱导肝星状细胞表达I型胶原基因。这些 细胞控制门静脉血流，产生过量的I型胶原 使伤口收缩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一级， 非-α因子和白细胞介素-6，它们是在 急性期，在启动肝星状细胞， 增殖并生成I型胶原。研究者的长期目标是 明确乙醇诱导肝纤维化的分子机制， 开发新的和更合理的抗纤维化疗法的基础上， 调查结果。在这个应用中，他们提出了一些实验来解开基本的 分子事件，其中急性期一般，和肿瘤坏死 特别是α因子和白细胞介素-6， 过程因此，PI将使用细胞和分子生物学的现代技术 为了解开参与肝细胞活化的信号转导途径， 星状细胞和建立途径，通过这些途径， 细胞因子增强乙醛的纤维化作用。而且 研究人员将测试秋水仙碱，一种抗炎药， 改善肝硬化的抗纤维化潜力对 要研究的参数。