Initiation and Regulation of Chronic Autoimmune Prostate Inflammation

描述（由申请人提供）：前列腺慢性非细菌性炎症与多种前列腺疾病相关，包括慢性前列腺炎-慢性盆腔疼痛综合征（CP-CPPS）、良性前列腺增生（BPH）和前列腺癌。CP-CPPS是影响任何年龄的男性的骨盆疼痛症状的疾病，据估计，50%的男性在其一生中经历过这种疾病。根据美国国立卫生研究院（National Institutes of Health）的数据，前列腺炎占所有年轻和中年男性泌尿生殖系统门诊的25%。类似地，慢性非细菌性炎症几乎总是存在于BPH组织中。BPH的慢性炎症过程与增生有关，可能与导致腺瘤形成的组织重塑有关。炎症也与前列腺癌有关。为了解决前列腺炎症的问题，开发了一种新的转基因小鼠模型。该模型在前列腺上皮细胞上表达模型抗原，提供了探测与前列腺炎症的启动和调节相关的因素所需的工具。初步数据证明了该模型的实用性，并确定了几个重要的因素，炎症的发展及其调节。这些数据为I型反应引发前列腺炎症的假设提供了基础，前列腺炎症扩展到包括与多种前列腺抗原反应的T细胞。此外，炎症由MDSC和Treg两者调节。为了解决这一假设，提出了三个具体目标：目标1。慢性自身免疫性前列腺炎症的启动和维持，目的2。骨髓源性抑制细胞在控制急性炎症和调节调节性T细胞中的作用和Aim 3。骨髓源性抑制细胞在慢性自身免疫性前列腺炎症调节中的作用追求拟议的研究将提供与前列腺炎症的启动和控制相关的因素的新信息。公共卫生相关性：前列腺的慢性非细菌性炎症与多种前列腺疾病相关，包括慢性前列腺炎-慢性盆腔疼痛综合征、良性前列腺增生和前列腺癌。炎症和前列腺癌之间的联系越来越被接受。因此，确定控制非细菌性慢性前列腺炎症所需的参数是非常重要的。

DESCRIPTION (provided by applicant): Chronic non-bacterial inflammation of the prostate is associated with multiple prostate diseases including chronic prostatitis-chronic pelvic pain syndrome (CP-CPPS), benign prostatic hyperplasia (BPH), and prostate cancer. CP-CPPS is disease of pelvic pain symptoms that affects men of any age and it is estimated that 50% of men experience the disorder during their lifetime. According to the National Institutes of Health, prostatitis accounts for 25% of all office visits involving the genitourinary system by young and middle-aged men. Similarly, chronic non-bacterial inflammation is virtually always present in BPH tissue. The chronic inflammatory processes in BPH are linked to hyperplasia and may be associated with tissue remodeling resulting in adenoma formation. Inflammation also is linked to prostate cancer. To address the problem of prostate inflammation a novel genetically modified mouse model was developed. The model, which expresses a model antigen on prostate epithelial cells provides the tools needed to probe factors linked to initiation and regulation of prostate inflammation. Preliminary data demonstrate the utility of the model and have identified several factors important to the development of inflammation and its regulation. These data provide a basis for the hypothesis that a Type I response initiates prostate inflammation, which expands to include T cells reactive with multiple prostate antigens. Further, inflammation is regulated by both MDSC and Treg. To address this hypothesis, three specific aims are proposed: Aim 1. Initiation and maintenance of chronic autoimmune prostate inflammation, Aim 2. Role of myeloid-derived suppressor cells in controlling acute inflammation and modulating regulatory T cells and Aim 3. Role of Myeloid-derived suppressor cells in the regulation of chronic autoimmune prostate inflammation. Pursuit of the proposed studies will provide novel information on the factors linked to initiation and control of prostate inflammation. PUBLIC HEALTH RELEVANCE: Chronic non-bacterial inflammation of the prostate is associated with multiple prostate diseases including chronic prostatitis-chronic pelvic pain syndrome, benign prostatic hyperplasia, and prostate cancer. The links between inflammation and prostate cancer are gaining acceptance. Therefore, it is of importance to define the parameters necessary for controlling non-bacterial chronic prostate inflammation.