Role of interferon beta in hypoxic intestinal epithelium

干扰素β在缺氧肠上皮中的作用

• 批准号: 6643351
• 负责人: Nancy Anne Louis
• 金额: $ 13.39万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-08-15 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6643351
• 关键词: disease /disorder model; gastrointestinal absorption /transport; gastrointestinal epithelium; gene induction /repression; hypoxia; hypoxia inducible factor 1; inflammation; inflammatory bowel diseases; interferon beta; laboratory mouse; membrane permeability; tissue /cell culture

DESCRIPTION (provided by applicant): Through study of the interaction between interferon beta (IFNbeta) and hypoxia-inducible factor 1 (HIF-1), important advances will be made in understanding epithelial regulation of the exposure of the immune system to contents of the intestinal lumen. It remains unclear how inflammation and hypoxia interact to influence the intestinal barrier in disease processes such as inflammatory bowel disease. The central hypothesis of this application is that hypoxia induces intestinal epithelial expression of INFbeta which functions in a feed-forward, autocrine manner to modulate HIF-1 expression and HIF-1 mediated responses to hypoxia, and this regulates the combined influence of hypoxia and inflammation on intestinal epithelial barrier function. The specific aims of the proposed project are to: (i) define the expression and biology of IFNbeta in hypoxic intestinal epithelium, (ii) define the role of IFNbeta with respect to HIF-1alpha-mediated responses to hypoxia in intestinal epithelium, and (iii) define the role of IFNbeta on HIF-1 expression and resultant changes in barrier function. Additional work examines the in vitro effects of IFNbeta in models of hypoxia and inflammatory bowel disease to explore its role in disease. These studies will expand our knowledge of the actions of IFNbeta in the intestinal epithelium and our understanding of the regulation of epithelial barrier function.

描述（由申请人提供）： 通过研究干扰素β（IFNBETA）和缺氧诱导因子1（HIF-1）之间的相互作用，将在理解免疫系统暴露于肠腔内容物的上皮调节时取得重要的进步。尚不清楚炎症和缺氧如何相互作用以影响诸如炎症性肠病等疾病过程中的肠道屏障。该应用的中心假设是，缺氧会诱导infbeta的肠上皮表达，该表达以馈送前向，自分泌的方式起作用，以调节HIF-1表达和HIF-1介导的对缺氧的反应，这调节了低氧和炎症对肠道上皮上皮上皮障碍的综合影响。拟议项目的具体目的是：（i）定义IFNBETA在缺氧性肠上皮上皮中的表达和生物学，（ii）定义IFNBETA在HIF-1Alpha介导的对HIF-1Alpha介导的对肠道上皮上皮中缺氧的反应方面的作用，（III）定义了IFNBETA的作用，并在hifnbeta nif-1表达中的作用。其他工作研究了IFNBETA在缺氧模型和炎症性肠病模型中的体外作用，以探索其在疾病中的作用。这些研究将扩大我们对IFNBETA在肠上皮的作用的了解，以及我们对上皮屏障功能调节的理解。