Bacterial modulation of gastrointestinal inflammation

胃肠道炎症的细菌调节

• 批准号: 6360310
• 负责人: STEVEN J CZINN
• 金额: $ 14.71万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-15 至 2005-09-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6360310
• 关键词: Helicobacter; Lactobacillus; disease /disorder model; gastrointestinal infection; immunization; inflammatory bowel diseases; laboratory mouse; microorganism immunology; mucosal immunity; pathologic process; peptic ulcer; virus diseases

Inflammatory bowel disease is a general term used to describe a group of chronic inflammatory disorders of the gastrointestinal tract. The two major clinical entities are ulcerative colitis and Crohn's disease. The two major clinical entities are ulcerative colitis and Crohn's disease. Clinically ulcerative colitis is confined to the large intestine, whereas Crohn's disease may affect any part of the gastrointestinal tract. The Crohn'S & Colitis Foundation of America estimates that about two million Americans suffer from inflammatory bowel disease, 300,000 of them in the pediatric age group. Despite traditional medical therapy, inflammatory bowel disease in children results in significant morbidity such as chronic abdominal pain, rectal bleeding, anemia, weight loss and growth stunt. While active investigation has yet to discover what causes inflammatory bowel disease, it is believed than an inappropriate host immune response to antigens (bacteria or flood) normally found in the gastrointestinal tract results in a state of chronic inflammation. It has been difficult to investigate the relationship between luminal bacteria and immune dysregulation due to the lack of a colitis model induced by a single well-defined organism. Infection of the normally abiotic mouse stomach with Helicobacter and Lactobacillus species provides an excellent model for the investigation of bacteria-associated chronic inflammation of the gastrointestinal mucosa. We have developed several murine models in which various bacterial species, that are either normally non pathogenic or are only mildly pathogenic, can induce a state of chronic mucosal inflammation. The inflammatory response can be generated either by deleting or adding various immunoregulatory cytokines, or by systemically immunizing mice prior to infection. Of particular importance is the observation that the mucosal inflammation is maintained even when organisms are no longer detectable by microbiological and molecular techniques. Using these models we will test the central hypotheses that chronic gastrointestinal inflammation results from an aberrant immune response to antigenic stimulus, consisting of normal gastrointestinal bacteria. We propose to investigate the relationship between mucosal bacteria and immune regulation in the early, intermediate and late stages of chronic mucosal inflammation using our unique models of gastric Helicobacter and Lactobacillus infection.

炎症性肠病是一种通用术语，用于描述胃肠道的一组慢性炎症性疾病。这两个主要的临床实体是溃疡性结肠炎和克罗恩病。 这两个主要的临床实体是溃疡性结肠炎和克罗恩病。临床上溃疡性结肠炎仅限于大肠，而克罗恩病可能会影响胃肠道的任何部分。美国克罗恩斯和结肠炎基金会估计，大约有200万美国人患有炎症性肠病，其中30万名小儿年龄段。尽管传统的药物治疗，但儿童的炎症性肠病仍会导致慢性腹痛，直肠出血，贫血，体重减轻和生长特技等明显的发病率。尽管积极的研究尚未发现导致炎症性肠病的原因，但据信它比通常在胃肠道中发现的对抗原（细菌或洪水）的不适当宿主免疫反应导致慢性炎症状态。由于缺乏由单个定义明确的生物引起的结肠炎模型，很难研究腔细菌与免疫失调之间的关系。正常情况下的小鼠胃中用螺旋杆菌和乳酸杆菌感染，为研究胃肠道粘膜的细菌相关慢性炎症提供了一个极好的模型。我们已经开发了几种鼠模型，其中各种细菌种类通常是非致病性的，或者仅是轻度致病性，可以诱导慢性粘膜炎症状态。炎症反应可以通过删除或添加各种免疫调节细胞因子或在感染之前对小鼠进行全身免疫免疫来产生。特别重要的是，即使微生物和分子技术不再检测到生物体，粘膜炎症也会保持粘膜炎症。使用这些模型，我们将测试中心假设，即慢性胃肠道炎症是由对抗原刺激的异常反应引起的，包括正常的胃肠道细菌。我们建议在慢性粘膜炎症的早期，中期和晚期使用我们独特的胃旋转杆菌和乳酸杆菌感染的模型研究粘膜细菌与免疫调节之间的关系。