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: 8545570
• 负责人: W ALLAN WALKER
• 金额: $ 135.25万
• 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/8545570
• 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.

本项目续期申请继续有一个狭窄的重点肠细胞的作用