INTESTINAL IMMUNE SYSTEM IN HOST-ENVIRONMENT INTERACTION

宿主与环境相互作用中的肠道免疫系统

• 批准号: 6890885
• 负责人: Martin Frederick KAGNOFF
• 金额: $ 160.09万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-11-01 至 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6890885
• 关键词: clinical research; gastrointestinal epithelium; microorganism immunology; mucosal immunity

The central theme of the Program Project is focused on defining the mechanisms that govem host inflammatory and immune responses at mucosal surfaces in the gastrointestinal tract. The four interrelated projects use microbial pathogens, microbial products, and environmental stress injuries as probes of host intestinal mueosal defense. The program applies state-of-the-art approaches and draws on strengths inherent in human and murine in vitro and in vivo model systems to explore key signaling pathways in host intestinal epithelial cells and macrophages that are required for innate immunity and cell survival. A major focus is placed on defining mechanisms by which bacteria, bacterial products, and mucosal injury signal intestinal epithelial cell and macrophage responses, and mechanisms that are important for the host response to infections with disease-causing noninvasive, minimally invasive and invasive pathogens. The Program brings together experienced investigators from the Departments of Medicine, Pharmacology and Pathology with significant expertise in immunology, molecular biology, biochemistry, and microbiology. Research Unit 1 investigates the functional role and importance of the transcription factor NF-kappaB in intestinal epithelial cells in vivo in regulating intestinal mueosal innate immune responses to microbial pathogens and in preventing epithelial cell apoptosis, as well as the role epithelial NF-kappaB plays in an in vitro model of epithelial cell wound healing. Research Unit 2 examines intestinal mucosal responses and mucosal defense mechanisms that govern the host's interaction with G. lamblia and C. parvum. Research Unit 3 examines epithelial cell signaling mechanisms that are activated by bacterial DNA and the mechanisms by which bacterial DNA can modulate intestinal mueosal innate immunity and mucosal inflammatory responses in vivo. Research Unit 4 examines the role of the transcription factor NF-kappaB in a model of intestinal isehemia reperfusion injury and the mechanisms by which NF-kappaB, together with p3 8 MAP kinase, governs macrophage death and survival in response to microbial products. The research projects are supported by four Cores: a Cell Culture and Assay Core, a Mouse Model Core, a Histopathology Core, and an Administrative Core.

该方案项目的中心主题是确定政府主持的机制 胃肠道粘膜表面的炎症和免疫反应。这四个相互关联的项目使用微生物病原体、微生物产品和环境应激损伤作为宿主肠道粘膜防御的探针。该计划应用最先进的方法，并利用人类和小鼠在体外和体内模型系统中固有的优势，探索宿主肠道上皮细胞和巨噬细胞中天然免疫和细胞生存所需的关键信号通路。主要的焦点放在确定细菌、细菌产物和粘膜损伤信号传递肠道信号的机制上。 上皮细胞和巨噬细胞的反应，以及对宿主对非侵袭性、微侵袭性和侵袭性病原体感染的反应至关重要的机制。该计划汇集了来自医学、药理学和病理学系的经验丰富的研究人员，他们在免疫学、分子生物学、生物化学和微生物学方面具有重要的专业知识。研究单元1调查体内肠道上皮细胞中转录因子NF-kappaB在调节肠道粘膜对微生物病原体的天然免疫反应中的功能作用和重要性，以及在预防 上皮细胞凋亡，以及上皮细胞核因子-kappaB在体外上皮细胞伤口愈合模型中所起的作用。研究单元2检查控制宿主与兰氏革兰氏菌和微小葡萄球菌相互作用的肠道粘膜反应和粘膜防御机制。研究单元3检查由细菌DNA激活的上皮细胞信号机制，以及细菌DNA在体内调节肠道粘膜天然免疫和粘膜炎症反应的机制。研究单元4研究了转录因子核因子-kappaB在肠缺血再灌注损伤模型中的作用，以及核因子-kappaB与p38MAPK一起调控巨噬细胞对微生物产物的死亡和存活的机制。研究项目由四个核心支持：细胞培养和检测核心、小鼠模型核心、组织病理学核心和管理核心。