H HEPATICUS--PATHOGENESIS OF INFLAMMATORY BOWEL DISEASE

肝螺杆菌——炎症性肠病的发病机制

• 批准号: 6342496
• 负责人: DAVID B SCHAUER
• 金额: $ 27.49万
• 依托单位: MASSACHUSETTS INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-01-01 至 2002-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6342496
• 关键词: Crohn's disease; Helicobacter; SCID mouse; T lymphocyte; bacterial cytopathogenic effect; bacterial genetics; cytokine; disease /disorder etiology; gene targeting; genetically modified animals; immunocytochemistry; inflammatory bowel diseases; laboratory mouse; pathologic process; ulcerative colitis; virulence

DESCRIPTION (Adapted from the applicant's abstract): The human inflammatory bowel diseases (IBDs), Crohn's disease and ulcerative colitis, are multifactorial disorders whose etiology remains unknown. Animal models have been developed to help understand the complex interaction between the immune system and intestinal antigens - particularly bacteria - which appear to be involved in the pathogenesis of disease. Infection with the mouse pathogen Helicobacter hepaticus has been associated with disease in mice which are genetically and/or immunologically predisposed to the development of IBD. H. hepaticus, like the human gastroduodenal pathogen H. pylori, expresses putative virulence factors which may contribute to chronic mucosal inflammation, epithelial cell proliferation, and an increased risk for cancer. The investigators propose to test the hypothesis that infection with H. hepaticus is sufficient for expression of disease in mice which are predisposed to the development of IBD. They also propose to identify the bacterial virulence factors of H. hepaticus which are involved in the pathogenesis of IBD in the mouse models. These studies will characterize the mechanism by which infection with a single bacterial species can affect expression of disease in mouse models of IBD. It is hoped that these studies will lead to the development of rational therapy for patients suffering from Crohn's disease and ulcerative colitis.

描述（改编自申请人的摘要）：人类炎症 肠道疾病（IBD）、克罗恩病和溃疡性结肠炎 病因尚不清楚的多因素疾病。 动物模型有 旨在帮助理解免疫系统之间复杂的相互作用 系统和肠道抗原 - 特别是细菌 - 这似乎是 参与疾病的发病机制。 小鼠病原体感染 肝螺杆菌与小鼠疾病有关，这些疾病 遗传和/或免疫学上易患 IBD。 肝螺杆菌与人类胃十二指肠病原体幽门螺杆菌一样，表达 可能导致慢性粘膜炎的假定毒力因子 炎症、上皮细胞增殖以及增加的风险 癌症。 研究人员建议检验感染的假设 肝螺杆菌足以在小鼠中表达疾病 易发生IBD。 他们还建议确定 肝螺杆菌的细菌毒力因子参与 IBD 在小鼠模型中的发病机制。 这些研究将表征 单一细菌种类感染影响的机制 IBD 小鼠模型中疾病的表达。 希望这些 研究将为患者制定合理的治疗方法 患有克罗恩病和溃疡性结肠炎。