Barrier Function of the GI Tract in Health and Disease

本计划项目续签申请继续侧重于肠上皮细胞在 微生物和肠毒素介导的刺激与免疫界面的粘膜屏障功能 效应器反应。肠上皮细胞是中心焦点，将就微生物的“串扰”进行研究。 免疫-上皮细胞相互作用，神经肽受体表达，发育不良 反应，以及微生物渗透的障碍。此续订申请由五个互动项目组成 由两个核心支持的项目，(1)行政和(2)异种/同种移植物移植，人 肠组织和成像核心主要在黏膜免疫实验室的一个位置 马萨诸塞州总医院-东部(BIdg 114)。项目1将审查NFkappaB/MyD88中的未到期债务 胎儿和成熟肠细胞中的先天反应基因和其他炎症途径有助于解释 早产儿过度的肠道炎症及氢化可的松和氢化可的松的试验预防 益生菌。项目2将研究促肾上腺皮质激素释放参与的机制。 神经肽及其受体激素族在大鼠粘膜炎症发展中的作用 对肠毒素和细菌病原体的反应。项目3将研究以下分子机制： 福氏志贺氏菌与肠上皮细胞在顶端或基侧膜域的相互作用导致急性 传染性结肠炎。项目4将确定全球环境基金--一种鸟核苷酸交换因子--H1的作用。 对于Rho，研究上皮细胞对病原体的反应，并研究这种反应的机制 交界标高。项目5将定义特定的细胞和分子机制，参与保护 布氏链霉菌对肠道感染和肠毒素介导的治疗作用 腹泻和肠道。炎症。研究人员。拥有细胞/分子生物学、微生物学、 肠道免疫和炎症。cand发育生物学将提供更好的理解 细菌性Gl感染和肠毒素介导的肠炎和NIAY的发病机制 预防和治疗胃肠道传染病的新治疗策略。

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.