Barrier Function of the GI Tract in Health and Disease

胃肠道的屏障功能在健康和疾病中的作用

• 批准号: 8214194
• 负责人: W ALLAN WALKER
• 金额: $ 142.88万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-04-01 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8214194
• 关键词: Barrier; Function; GI; Tract; Health

DESCRIPTION (provided by applicant): This Program Project renewal application continues to have a narrow focus on the role of enterocytes in mucosal barrier function at the interface between microbial and enterotoxin-mediated stimuli and immune effector responses. The enterocyte is the central focus and will be studied with regard to microbial "crosstalk" and immune-epithelial cell interactions, neuropeptide receptor expression, inappropriate developmental responses, and a barrier to microbial penetration. This renewal application consists of five interactive projects supported by two cores, (1) An Administrative and (2) Xenograft/lsograft Transplant, human intestinal tissue and imaging core principally in one location in the Mucosal Immunology Laboratory at the Massachusetts General Hospital-East (BIdg 114). Project 1 will examine immaturities in NFkappaB/MyD88 innate response genes and in other inflammatory pathways in fetal vs. mature enterocytes to help explain excessive intestinal inflammation in prematures and test maturational prevention with hydrocortisone and probiotics. Project 2 will examine the mechanisms involved in the participation of corticotrophin releasing hormone family of neuropeptides and their receptors in the development of mucosal inflammation in response to enterotoxins and bacterial pathogens. Project 3 will study the molecular mechanisms underlying S. flexneri-intestinal epithelial interactions at the apical or basolateral membrane domain that lead to acute infectious colitis. Project 4 will determine the role of GEF-H1, a guanine nucleotide exchange factor (GEF) for Rho, on epithelial cell responses to pathogens and examine the mechanism of this response at the tight junctional level. Project 5 will define specific cellular and molecular mechanisms involved in the protective and therapeutic effects of the probiotic agent .S.boulardii in enteric infections and enterotoxin-mediated diarrhea and intestinal inflammation. Investigators with disciplines in cell/molecular biology, microbiology, intestinal immunity and inflammation and developmental biology will provide a better understanding of the pathogenesis of bacterial Gl infections and enterotoxin-mediated intestinal inflammation and may lead to new therapeutic strategies in preventing and treating infectious diseases in the Gl tract. PUBLIC HEALTH RELEVANCE: This Program Project examines how colonizing bacteria stimulate intestinal host defense and prevents inflammation by pathogens and their toxins as a translation contribution. Observations made may lead to strategies for prevention of intestinal infectious disease. TABLE OF CONTENTS Overall Description 2

描述（由申请人提供）：本计划项目更新申请继续关注肠上皮细胞在微生物和肠毒素介导的刺激与免疫效应器应答之间界面处的粘膜屏障功能中的作用。肠上皮细胞是中心焦点，将研究微生物的“串扰”和免疫上皮细胞的相互作用，神经肽受体的表达，不适当的发育反应，和微生物渗透的障碍。本更新申请包括由两个核心支持的五个交互式项目，（1）管理和（2）异种移植/同种移植移植、人肠组织和成像核心，主要位于马萨诸塞州总医院东部（BIdg 114）的粘液瘤免疫学实验室。项目1将检查胎儿与成熟肠细胞中NF κ B/MyD 88先天反应基因和其他炎症途径的不成熟性，以帮助解释早产儿的过度肠道炎症，并测试氢化可的松和益生菌的成熟预防。项目2将研究促肾上腺皮质激素释放激素家族的神经肽及其受体参与肠毒素和细菌病原体引起的粘膜炎症发展的机制。项目3将研究S.福氏肠上皮细胞在顶端或基底侧膜域的相互作用，导致急性感染性结肠炎。项目4将确定GEF-H1（Rho的鸟嘌呤核苷酸交换因子（GEF））在上皮细胞对病原体反应中的作用，并在紧密连接水平上研究这种反应的机制。项目5将定义益生菌制剂布拉氏酵母菌在肠道感染和肠毒素介导的腹泻和肠道炎症中的保护和治疗作用所涉及的特定细胞和分子机制。具有细胞/分子生物学、微生物学、肠道免疫和炎症以及发育生物学学科的研究者将提供对细菌GI感染和肠毒素介导的肠道炎症的发病机制的更好理解，并且可能导致预防和治疗GI道中的感染性疾病的新的治疗策略。 公共卫生关系：这个项目研究了殖民细菌如何刺激肠道宿主防御，并防止病原体及其毒素作为翻译贡献的炎症。所做的观察可能会导致肠道传染病的预防策略。 目录 总体描述 2