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

描述（由申请人提供）：前列腺炎是一种常见疾病，影响2%-10%的男性在他们生命中的某个时候。急性细菌性前列腺炎、慢性细菌性前列腺炎或无症状炎性前列腺炎在5%-10%的前列腺炎病例中被诊断，而慢性前列腺炎/慢性骨盆疼痛综合征（CP/CPPS）占其余病例的90-95%。慢性前列腺炎/慢性骨盆疼痛综合征可进一步表征为炎性（IIIA类）或非炎性（IIIB类），这分别取决于前列腺液中是否存在白细胞。IIIA或IIIB类前列腺炎的病因尚不完全清楚。在IIIA和IIIB类患者的前列腺分泌物中没有可培养的微生物，这表明该疾病不是由于感染因子引起的;然而，研究表明，在CP/CPPS男性的前列腺或前列腺周围组织中发现了高频率的细菌16 S核糖体DNA（rDNA）。前列腺分泌物中16 S rDNA的存在与炎性细胞之间也存在高度相关性。这两个结果表明，隐蔽的，非常挑剔的，或不可培养的细菌可能参与CP/CPPS。也可以想象，前列腺分泌物中不存在的细胞内细菌可能提供感染的储存库和慢性炎症的来源。 大量的研究表明，E.大肠杆菌能够侵入膀胱上皮细胞，并建立细胞内菌落，可导致复发性尿路感染。我们已经开发了一种方法来评估E。coli体外侵袭前列腺上皮细胞，观察E.大肠杆菌菌株。细胞侵袭也依赖于正常血清中存在的因子。本文提出的第一个具体研究目标是阐明E.大肠杆菌毒力因子;大肠杆菌为前列腺炎侵袭所需分离株。第二个具体的目标是确定上皮细胞在E.大肠杆菌侵袭。这些研究的结果将检验前列腺上皮细胞的侵袭和随后的炎症介质释放可能是CP/CPPS的基础的假设。 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最常见的形式，并导致显著的患者发病率。虽然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存在隐蔽细菌，这可能是持续感染和炎症的来源。因此，本研究的目的是阐明毒力因子E。大肠杆菌菌株，可以侵入前列腺上皮细胞，并确定入侵后细胞释放的炎症介质。

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.