Etiological role of Epithelial Cell-Invasive E. coli in Chronic Prostatitis

上皮细胞侵袭性大肠杆菌在慢性前列腺炎中的病因学作用

基本信息

批准号：
7897044
负责人：
WALTER J HOPKINS
金额：
$ 18.56万
依托单位：
UNIVERSITY OF WISCONSIN-MADISON
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-06-07 至 2012-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7897044
关键词：
Accounting Acute Acute Prostatitis Address Adult Affect Antibodies Bacteria Bacterial Prostatitis Bladder Categories Cells Chlamydia Chronic Chronic Prostatitis Clinical Code DNA Data Development Diagnosis Disease Enterococcus Epithelial Cells Escherichia coli Etiology Frequencies Genes Genitourinary system In Vitro Individual Infection Infectious Agent Inflammation Inflammation Mediators Inflammatory Inflammatory Response Invaded Klebsiella Lesion Leukocytes Life Link Liquid substance Massage Mediator of activation protein Methods Microbe Modeling Morbidity - disease rate Mus Mycoplasma Patients Periprostatic Play Property Prostate Prostatic Proteus Pseudomonas Recurrence Reporting Research Ribosomal DNA Role Sampling Seminal fluid Serum Source Staining method Stains Stimulus Symptoms Testing Time Tissues Trichomonas Ureaplasma Urinary tract infection Urine Uropathogenic E. coli Urothelial Cell Virulence Virulence Factors base chemokine chronic pelvic pain cytokine insight intestinal epithelium men microorganism mutant pathogenic Escherichia coli prostatitis public health relevance research study

项目摘要

DESCRIPTION (provided by applicant): Prostatitis is a common disease affecting 2%-10% of men at some point in their lives. Acute bacterial prostatitis, chronic bacterial prostatitis, or asymptomatic inflammatory prostatitis is diagnosed in 5%-10% of prostatitis cases, while chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) accounts for the remaining 90-95% of cases. Chronic prostatitis/chronic pelvic pain syndrome can be further characterized as inflammatory (Category IIIA) or non-inflammatory (Category IIIB) depending on whether leukocytes are present or absent, respectively, in prostatic fluid. The etiologies of categories IIIA or IIIB prostatitis are not completely known. The absence of culturable microorganisms in prostatic secretions of category IIIA and IIIB patients suggests that the disease is not due to an infectious agent; however, studies have shown that bacterial 16S ribosomal DNA (rDNA) was found at a high frequency in prostatic or periprostatic tissue from men with CP/CPPS. There was also a high correlation between the presence of 16S rDNA and inflammatory cells in prostatic secretions. These two results indicate that cryptic, extremely fastidious, or unculturable bacteria may be involved in CP/CPPS. It is also conceivable that intracellular bacteria, which would not be present is prostatic secretions, may provide a reservoir of infection and source of chronic inflammation. A large number of studies have shown that E. coli are capable of invading bladder epithelial cells and establishing intracellular colonies that can cause recurrent urinary tract infections. We have developed a method to assess the ability of E. coli to invade prostate epithelial cells in vitro and observe differences in the invasiveness of E. coli strains. Cellular invasion is also dependent on factors present in normal serum. The first specific aim of research proposed here is to elucidate the E. coli virulence factors in E. coli prostatitis isolates required for invasion. The second specific aim is to define inflammatory mediators released by epithelial cells after E. coli invasion. Results from these studies will test the hypothesis that invasion of prostate epithelial cells and subsequent release of inflammatory mediators may be the basis for CP/CPPS. PUBLIC HEALTH RELEVANCE: Chronic prostatitis/chronic pelvic pain syndrome is the most common form of prostatitis and causes significant patient morbidity. While the etiology of the disease is unknown, there is evidence of cryptic bacteria in patient's prostate tissue, which may be a source of ongoing infection and inflammation. The objectives of the research proposed are thus to elucidate virulence factors E. coli strains that can invade prostate epithelial cells and to identify inflammatory mediators released by cells after invasion.

描述（由申请人提供）：前列腺炎是一种常见的疾病，在生活中的某个时候影响了2％-10％的男性。急性细菌前列腺炎，慢性细菌前列腺炎或无症状炎症前列腺炎在5％-10％的前列腺炎病例中被诊断出来，而慢性前列腺炎/慢性骨盆疼痛综合征（CP/CPP）占病例剩余90-95％的剩余90-95％。慢性前列腺炎/慢性骨盆疼痛综合征可以进一步以炎症性（IIIIA类）或非炎症性（IIIB类）（IIIB类）来表征，具体取决于白细胞在前列腺液中分别存在还是不存在。 IIIA类或IIIB前列腺炎类的病因并不完全清楚。 IIIA类和IIIB患者的前列腺分泌物中缺乏可培养的微生物，这表明该疾病不是由于传染剂引起的。然而，研究表明，来自CP/CPP的男性的前列腺或腹膜组织中的细菌16S核糖体DNA（rDNA）在高频中发现。在前列腺分泌中，16S rDNA的存在与炎症细胞之间也存在很高的相关性。这两个结果表明，CP/CPP可能涉及神秘，极为挑剔或无法培养的细菌。还可以想象，不存在的细胞内细菌是前列腺分泌物，可能会提供感染的储层和慢性炎症的来源。大量研究表明，大肠杆菌能够入侵膀胱上皮细胞并建立可能引起复发尿路感染的细胞内菌落。我们开发了一种评估大肠杆菌在体外侵袭前列腺上皮细胞的能力的方法，并观察到大肠杆菌菌株的侵入性差异。细胞侵袭还取决于正常血清中存在的因素。此处提出的研究的第一个具体目的是阐明大肠杆菌前列腺炎分离株所需的大肠杆菌毒力因子。第二个具体目的是定义大肠杆菌入侵后上皮细胞释放的炎症介质。这些研究的结果将检验以下假设：前列腺上皮细胞的侵袭和随后释放炎症介质可能是CP/CPP的基础。公共卫生相关性：慢性前列腺炎/慢性骨盆疼痛综合征是前列腺炎的最常见形式，并引起严重的患者发病率。尽管该疾病的病因尚不清楚，但有证据表明患者的前列腺组织中有神秘的细菌，这可能是持续感染和炎症的根源。因此，提出的研究的目的是阐明可以侵入前列腺上皮细胞并鉴定细胞侵入后释放的炎症介质的大肠杆菌菌株的毒力因子。