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: 8337712
• 负责人: W ALLAN WALKER
• 金额: $ 140.24万
• 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/8337712
• 关键词: Acute; Affect; Bacteria; Bacterial Toxins; Cell Communication; Cells; Colitis; Communicable Diseases; Corticotropin-Releasing Hormone; Development; Developmental Biology; Diarrhea; Discipline; Disease; Enteral; Enterocytes; Enterotoxins; Epithelial; Epithelial Cells; Family; Gastrointestinal tract structure; General Hospitals; Genes; Guanine Nucleotide Exchange Factors; Health; Host Defense; Human; Hydrocortisone; Image; Immune; Immunity; Infection; Inflammation; Inflammatory; Inflammatory disease of the intestine; Intestinal Diseases; Intestines; Laboratories; Lead; Location; Lymphoid; Massachusetts; Mediating; Microbiology; Molecular; Molecular Biology; Mucositis; Nerve; Neuropeptide Receptor; Neuropeptides; Pathogenesis; Pathway interactions; Penetration; Play; Prevention; Prevention strategy; Probiotics; Research Personnel; Role; Shigella flexneri; Site; Stimulus; Testing; Therapeutic Effect; Tissues; Toxin; Translations; Transplantation; Xenograft procedure; apical membrane; basolateral membrane; enteric pathogen; fetal; interdisciplinary approach; microbial; novel therapeutics; pathogen; premature; prevent; programs; protective effect; receptor; receptor expression; response; rho

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) a Xenograft/lsograft Transplant, human intestinal tissue and imaging core principally in one location in the Mucosal Immunolog 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 corticotropin-releasing hormone family of neuropeptides and their receptors in the development of mucosal inflammation in response to enterotoxiris and bacterial pathogens. Project 3 will study the molecular mechanisms underiying S. flexneri-intestinal epithelial interactions at the apical or basolateral membrane domain that lead to acute infectious colitis. Project 4 will determinethe 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 molecularmechanisms 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.cand developmental biology will provide a better understanding of the pathogenesis of bacterial Gl infections and enterotoxin-mediated intestinal inflammation and niay lead to new therapeutic strategies in preventing and treating infectious diseases in the Gl tract.

该计划项目更新申请继续关注肠上皮细胞在以下方面的作用： 在微生物和肠毒素介导的刺激与免疫之间的界面处的粘膜屏障功能 效应子反应肠上皮细胞是中心焦点，将研究微生物的“串扰”。 免疫-上皮细胞相互作用、神经肽受体表达、不适当的发育 反应，以及微生物渗透的屏障。此更新应用程序包括五个交互式 由两个核心支持的项目，（1）行政和（2）异种移植/同种移植，人类 肠组织和成像核心主要在一个位置的粘液免疫实验室， 马萨诸塞州东总医院（BIdg 114）。项目1将检查NF kappaB/MyD 88中的未成熟度 先天反应基因和其他炎症途径在胎儿与成熟肠上皮细胞，以帮助解释 早产儿肠道过度炎症和氢化可的松测试成熟预防， 益生菌项目2将研究参与促肾上腺皮质激素释放的机制。 激素家族神经肽及其受体在粘膜炎症发生中的作用 对肠毒素和细菌病原体的反应。项目3将研究 S.福氏肠上皮细胞在顶端或基底外侧膜域的相互作用，导致急性 传染性结肠炎项目4将确定GEF-H1（一种鸟嘌呤核苷酸交换因子）的作用 对于Rho，上皮细胞对病原体的反应，并检查这种反应的机制， 交界水平。项目5将定义参与保护性免疫的特定细胞和分子机制。 和益生菌剂布拉酵母菌在肠道感染和肠毒素介导的 腹泻和尿道炎。细胞/分子生物学、微生物学、 肠免疫和炎症。cand发育生物学将提供一个更好的理解， 细菌GI感染和肠毒素介导的肠道炎症的发病机制， 预防和治疗胃肠道感染性疾病的新治疗策略。