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: 6128654
• 负责人: MARCOS ROJKIND
• 金额: $ 23.25万
• 依托单位: ALBERT EINSTEIN COLLEGE OF MEDICINE
• 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 2005-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6128654
• 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《调查者摘要》)：酒精诱导的肝脏 肝硬变是世界范围内主要的死亡原因，占50%以上 占所有死于肝硬变的人的百分比。目前还没有得到证实的治疗方法。 致命的疾病，因此，人们正在进行多种尝试，以开发 新型抗纤维化药物的研究进展 疾病的病理生理学。地方性和系统性事件都起着关键作用 在肝硬变的发展过程中。在地方层面上，会导致纤维化和 诱导肝星状细胞表达I型胶原基因。这些 细胞控制门脉血流，产生过量的I型胶原 和收缩的伤口。肝巨噬细胞和炎性细胞产生 激活肝脏起关键作用的细胞因子和生长因子 星状细胞形成疤痕组织。在系统层面上，总体反应 对非因子-α和白介素6的影响，这两种物质是在 急性期，在启动肝星状细胞 增殖并产生I型胶原。调查员的长期目标是 明确乙醇诱导肝纤维化的分子机制 在此基础上开发新的更合理的抗纤维化治疗方法 调查结果。在这项申请中，他们提出了一些实验来解开基本的 分子事件，由此导致的急性期和肿瘤坏死 尤其是因子-α和白介素6，导致了肝纤维化。 进程。因此，PI将使用细胞和分子生物学的现代技术 解开参与肝脏活化的信号转导通路 星状细胞和建立急性期通过的途径 细胞因子可增强乙醛的促纤维化作用。此外， 调查人员将测试秋水仙素，一种抗炎药物 改善活动性肝硬变的抗纤维化潜力对 待调查的参数。