The Impact of Bowel Inflammation on Local Cystitis

肠道炎症对局部膀胱炎的影响

基本信息

批准号：
7571854
负责人：
YI LUO
金额：
$ 11.5万
依托单位：
UNIVERSITY OF IOWA
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-09-15 至 2013-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7571854
关键词：
Afferent Neurons Animal Model Animals Back Basic Science Behavior Biological Biological Markers Bladder CD4 Positive T Lymphocytes CD8B1 gene Calmette-Guerin Bacillus Chronic Clinical Condition Cromolyn Sodium Crossbreeding Cystitis Development Diagnosis Disease Enterocolitis Exhibits Functional disorder Future Gene Expression Goals High Prevalence Histopathology Human Immunosuppressive Agents Inflammation Inflammatory Interstitial Cystitis Intervention Intestines Irritable Bowel Syndrome Light Localized Mast Cell Stabilizer Messenger RNA Modeling Molecular Molecular Profiling Mus Neurogenic Bladder Neurogenic Inflammation Neurons Neuropeptides Oral Pain Pathogenesis Patients Peptides Proteins RDP58 Research Serum Specimen Symptoms T-Lymphocyte Testing Therapeutic Agents Tissues Transgenic Mice Urination Urine base chemokine clinically relevant cytokine immunopathology improved intraperitoneal intravesical mast cell novel painful bladder syndrome response urologic

项目摘要

Interstitial cystitis/painful bladder syndrome (IC/PBS) has been suggested to be a local manifestation of a systemic chronic inflammatory disease or condition. Studies have shown that as many as 50% of IC/PBS patients have irritable bowel syndrome (IBS) whereas a similar high prevalence of IC/PBS presents in IBS patients. Animal studies have demonstrated that induction of colonic inflammation could cause sensory neurons in the bladder to release neuropeptides, leading to neurogenic bladder inflammation. However, despite these observations, the impact of co-presence of IBS on IC/PBS remains unclear. Based on clinical and animal studies, we hypothesize that both localized IC/PBS and IC/PBS with IBS could exhibit similar urological dysfunctions and pain symptoms; however, they are distinctive in pathophysiology, which can be distinguished by immunological analysis at the molecular and cellular levels. To test this hypothesis, we will conduct the following three specific aims: Specific Aim 1) To establish a cystitis model with concomitant bowel inflammation, and determine the impact of bowel inflammation on local cystitis; Specific Aim 2) To determine the impact of bowel inflammation on bladder response to intravesical therapeutic agents, and to develop effective therapy for cystitis with bowel inflammation; Specific Aim 3) To establish the inflammatory and gene expression profiles for localized IC/PBS and IC/PBS with IBS, and determine the impact of concomitant IBS on bladder expression of inflammatory/neuroinflammatory substances. We will cross our newly developed URO-OVA mice (a novel bladder inflammation model) with Fabpl-OVA mice (an enterocolitis model) to generate a new cystitis model with concomitant bowel inflammation. We will then use both URO-OVA mice and the crossed URO/Fabpl-OVA mice (i.e. localized cystitis vs. cystitis with bowel inflammation) to mimic human IC/PBS and IC/PBS with IBS to fulfill our study goals in animal models. We will also analyze human biological specimens to establish inflammatory and gene expression profiles for IC/PBS both with and without IBS. Key factors will be identified and new biomarkers will be explored. Successful completion of this study will improve our understanding of the differential immunopathology between localized IC/PBS and IC/PBS with bowel inflammation, provide a useful systemic IC/PBS model, and aid future development of new diagnosis and treatment for IC/PBS patients

间质性膀胱炎/膀胱疼痛综合征（IC/PBS）被认为是膀胱炎的局部表现。全身性慢性炎症性疾病或病症。研究表明，多达 50% 的 IC/PBS 患者患有肠易激综合征 (IBS)，而 IBS 中 IC/PBS 的患病率也很高患者。动物研究表明，诱导结肠炎症可能会导致感觉膀胱中的神经元释放神经肽，导致神经源性膀胱炎症。然而，尽管有这些观察结果，IBS 共存对 IC/PBS 的影响仍不清楚。根据临床和动物研究中，我们假设局部 IC/PBS 和具有 IBS 的 IC/PBS 可能表现出相似的泌尿系统功能障碍和疼痛症状；然而，它们在病理生理学上是独特的，这可以通过分子和细胞水平的免疫学分析来区分。为了检验这个假设，我们将进行以下三个具体目标：具体目标 1) 建立膀胱炎模型并伴有肠道炎症，并确定肠道炎症对局部膀胱炎的影响；具体目标 2) 至确定肠道炎症对膀胱内治疗药物反应的影响，并开发治疗伴有肠道炎症的膀胱炎的有效疗法；具体目标 3) 确定炎症以及局部 IC/PBS 和 IC/PBS 伴 IBS 的基因表达谱，并确定伴随的 IBS 对膀胱炎症/神经炎症物质表达的影响。我们将跨越我们的新开发的 URO-OVA 小鼠（一种新型膀胱炎症模型）与 Fabpl-OVA 小鼠（一种新型膀胱炎症模型）小肠结肠炎模型）生成伴随肠道炎症的新膀胱炎模型。然后我们将使用 URO-OVA 小鼠和杂交 URO/Fabpl-OVA 小鼠（即局限性膀胱炎与肠道膀胱炎）炎症）来模拟人类 IC/PBS 和带有 IBS 的 IC/PBS，以实现我们在动物模型中的研究目标。我们还将分析人类生物样本，以建立炎症和基因表达谱 IC/PBS 具有和不具有 IBS。将确定关键因素并探索新的生物标志物。这项研究的成功完成将提高我们对差异免疫病理学的理解在局部 IC/PBS 和具有肠道炎症的 IC/PBS 之间进行比较，提供有用的全身 IC/PBS 模型，并帮助未来开发针对 IC/PBS 患者的新诊断和治疗方法