THE ROLE OF BACTERIAL PEPTIDES IN CHRONIC INTESTINAL INFLAMMATION

细菌肽在慢性肠道炎症中的作用

• 批准号: 8357063
• 负责人: Caroline B Appleyard
• 金额: $ 12.33万
• 依托单位: PONCE SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-01-01 至 2011-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8357063
• 关键词: Abdominal Pain; Animal Model; Anti-Inflammatory Agents; Anti-inflammatory; Antibiotic Therapy; Bacteria; Basic Science; Body Weight decreased; Chronic; Chronic Phase; Clinical; Colitis; Colon; Complex; Crohn' s disease; Diarrhea; Effectiveness; Epithelial; Equilibrium; FPR1 gene; Funding; Future; Gene Expression; Grant; Hemorrhage; Human; Immune response; Immune system; Inflammation; Inflammatory; Inflammatory Bowel Diseases; Inflammatory Response; Inflammatory disease of the intestine; Intestines; Ion Transport; Knowledge; Measures; Modeling; N-Formylmethionine Leucyl-Phenylalanine; National Center for Research Resources; Neuromodulator; Pathogenesis; Pathway interactions; Patients; Peptides; Phase; Principal Investigator; Relapse; Research; Research Infrastructure; Resources; Role; Source; Symptoms; Testing; Therapeutic Intervention; Tissue Viability; Transport Process; Ulcer; Ulcerative Colitis; United States National Institutes of Health; cell motility; cost; cytokine; medical schools; methionyl-leucyl-phenylalanine; pathogen; programs; response; Abdominal Pain; Animal Model; Anti-Inflammatory Agents; Anti-inflammatory; Antibiotic Therapy; Bacteria; Basic Science; Body Weight decreased; Chronic; Chronic Phase; Clinical; Colitis; Colon; Complex; Crohn' s disease; Diarrhea; Effectiveness; Epithelial; Equilibrium; FPR1 gene; Funding; Future; Gene Expression; Grant; Hemorrhage; Human; Immune response; Immune system; Inflammation; Inflammatory; Inflammatory Bowel Diseases; Inflammatory Response; Inflammatory disease of the intestine; Intestines; Ion Transport; Knowledge; Measures; Modeling; N-Formylmethionine Leucyl-Phenylalanine; National Center for Research Resources; Neuromodulator; Pathogenesis; Pathway interactions; Patients; Peptides; Phase; Principal Investigator; Relapse; Research; Research Infrastructure; Resources; Role; Source; Symptoms; Testing; Therapeutic Intervention; Tissue Viability; Transport Process; Ulcer; Ulcerative Colitis; United States National Institutes of Health; cell motility; cost; cytokine; medical schools; methionyl-leucyl-phenylalanine; pathogen; programs; response

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Despite decades of research, the basic pathogenic mechanisms involved in inflammatory bowel disease (IBD) are still unknown. Many therapies are currently available, but there are still no cures for Crohn¿s disease and ulcerative colitis whose major symptoms include abdominal pain, ulceration, bleeding, weight loss, and diarrhea. Clinical observations have suggested that intestinal bacteria might trigger, and perhaps exacerbate, the inflammatory response. It is more likely, however, that the pathogenesis of IBD is not associated with any specific pathogen per se, but with bacterial products, some of which have been detected in the gut of patients. The central hypothesis of this proposal is that bacterial peptides such as N-formyl-methionyl-leucyl-phenylalanine (fMLP) may influence the inflammatory response in the relapse phase of chronic colitis through an increase in gene expression of pro- inflammatory cytokines, and through a decrease in tissue viability and alteration of motility. FMLP has been found in the intestine of patients, and there is evidence that epithelial transporters for this molecule are abnormally expressed in inflammation. Recent discoveries suggest that a dysregulated immune response is directed against the normal bacterial flora in IBD, but little is known about the complex interactions occurring between pro- and anti-inflammatory cytokines. The central hypothesis will be systematically tested as follows: 1. The role of fMLP in a chronic ¿reactivated¿ model of colitis and its ability to cause reactivation by itself will be investigated (Hypothesis: fMLP can initiate the relapse of inflammation in this model and contribute to the pathogenesis of colitis in the relapse phase.). 2. The levels of various cytokines after administration of fMLP in chronic ¿reactivated¿ colitis will be measured (Hypothesis: If damage is increased by fMLP, then an increase in pro-inflammatory cytokines, or a change in the balance of the immune system, will be observed.). 3. The role of fMLP in the secretory responses and motility changes of the intestine in chronic ¿reactivated¿ colitis will be evaluated (Hypothesis: Alterations of cytokine levels and release of neuromodulators by administration of fMLP in a reactivated model of animal colitis may alter the ion transport processes and contractile responses of the colon, thus contributing to the diarrhea observed in the human condition.). Knowledge of the immunoregulatory pathways evoked in response to bacterial peptides in chronic colitis will provide new avenues for potential therapeutic intervention in the future, and will solve the controversy over the effectiveness of antibiotic treatment.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 尽管进行了数十年的研究，但炎症性肠病（IBD）涉及的基本致病机制仍然未知。目前有许多疗法可用，但是克罗恩病和溃疡性结肠炎仍然没有治疗方法，其主要症状包括腹痛，溃疡，出血，体重减轻和腹泻。临床观察结果表明，肠道细菌可能会触发，甚至加剧炎症反应。然而，更有可能IBD的发病机理与任何特定的病原体本身无关，而与细菌产物相关，其中有些在患者的肠道中被检测到。 该提议的中心假设是，诸如N-甲基甲基二甲基 - 葡萄糖基 - 苯丙氨酸（FMLP）等细菌可能会通过增加基因炎性细胞因子的基因表达，以及通过降低组织稳定性和运动能力的降低，从而影响慢性结肠炎的接力阶段的炎症反应。在患者肠中发现了FMLP，有证据表明该分子的上皮转运蛋白在炎症中交替表达。最近的发现表明，针对IBD中正常细菌菌群的免疫增强反应失调，但对促疾病和抗炎细胞因子之间发生的复杂相互作用知之甚少。中心假设将在以下情况下进行系统的检验：1。fmlp在慢性«eveDectectectect的慢性中的作用。施用FMLP后各种细胞因子在慢性»慢性细胞炎后的水平将得到测量（假设：假设：如果FMLP增加了损害，则会增加损害，然后将损害增加一个损害，即在系统中的增加，或者是一个差异，或者是一个差异。 3。将评估FMLP在慢性重新激活的肠道秘密反应和运动变化中的作用（假设：细胞因子水平的改变以及通过在重新激活的动物结肠模型中通过施用FMLP释放神经调节剂的释放，可能会改变人类的结肠和分散性反应，从而改变人类的贡献。 了解慢性结肠炎细菌诱发的免疫调节途径的知识将为未来潜在的治疗干预提供新的途径，并将解决有关抗生素治疗有效性的争议。