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

描述(申请人提供)：前列腺炎是一种常见疾病，2%-10%的男性会在一生中的某个时候受到影响。5%-10%的前列腺炎病例诊断为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，其余90%-95%的病例诊断为慢性前列腺炎/慢性盆腔疼痛综合征(CP/CPPS)。慢性前列腺炎/慢性盆腔疼痛综合征可进一步分为炎症性(IIIA类)或非炎症性(IIIB类)，这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，这表明该病不是由感染性因素引起的；然而，研究表明，在CP/CPPS患者的前列腺或前列周组织中发现细菌16S核糖体DNA(RDNA)的频率很高。前列腺炎性细胞与前列腺液中16S rDNA的存在也高度相关。这两个结果表明，CP/CPPS可能与隐蔽的、极其挑剔的或不可培养的细菌有关。同样可以想象的是，前列腺分泌物中不存在的细胞内细菌可能是感染的蓄水池和慢性炎症的来源。大量研究表明，大肠埃希菌能够侵袭膀胱上皮细胞，并建立细胞内克隆，可导致反复的尿路感染。我们已经开发了一种方法来评估大肠杆菌在体外侵袭前列腺上皮细胞的能力，并观察不同菌株侵袭力的差异。细胞侵袭也依赖于正常血清中存在的因素。本文提出的研究的第一个具体目的是阐明入侵所需的大肠杆菌前列腺炎分离株中的大肠杆菌毒力因子。第二个具体目标是确定大肠杆菌入侵后上皮细胞释放的炎性介质。这些研究的结果将检验这一假说，即前列腺上皮细胞的侵袭和随后释放的炎性介质可能是CP/CPPS的基础。 与公共卫生相关：慢性前列腺炎/慢性盆腔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之一。因此，这项研究的目的是阐明可以入侵前列腺上皮细胞的致病因子大肠杆菌菌株，并识别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.