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: 7219419
• 负责人: Martin Frederick KAGNOFF
• 金额: $ 160.82万
• 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 2009-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7219419
• 关键词: INTESTINAL; IMMUNE; SYSTEM; HOST; ENVIRONMENT

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.

该计划项目的中心主题是重点确定政府主办的机制 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、微生物产物和环境应激损伤作为宿主肠道粘膜防御的探针。该计划采用最先进的方法，并利用人类和小鼠体外和体内模型系统的固有优势，探索宿主肠上皮细胞和巨噬细胞中先天免疫和细胞存活所需的关键信号通路。一个主要的重点放在确定机制，细菌，细菌产品，和粘膜损伤的信号肠 上皮细胞和巨噬细胞反应，以及对宿主对致病性非侵入性、最小侵入性和侵入性病原体感染的反应重要的机制。该计划汇集了来自医学，药理学和病理学部门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研究了转录因子NF-κ B在体内肠上皮细胞中调节肠道黏膜对微生物病原体的先天免疫应答和预防肠道疾病中的功能作用和重要性。 上皮细胞凋亡，以及上皮NF-κ B在上皮细胞伤口愈合的体外模型中所起的作用。第二研究单元探讨肠道粘膜反应和粘膜防御机制，管理主机的相互作用与G。lamblia和C.小的研究单元3研究由细菌DNA激活的上皮细胞信号传导机制以及细菌DNA在体内调节肠粘膜先天免疫和粘膜炎症反应的机制。研究单元4研究了转录因子NF-κ B在肠缺血再灌注损伤模型中的作用，以及NF-κ B与p3 8 MAP激酶一起控制巨噬细胞死亡和存活以响应微生物产物的机制。研究项目由四个核心支持：细胞培养和测定核心，小鼠模型核心，组织学核心和行政核心。