Initiation and Regulation of Chronic Autoimmune Prostate Inflammation

慢性自身免疫性前列腺炎症的引发和调节

基本信息

批准号：
7713628
负责人：
Timothy L. Ratliff
金额：
$ 32.51万
依托单位：
PURDUE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-30 至 2011-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7713628
关键词：
Accounting Acute Address Affect Age Animal Model Anti-Inflammatory Agents Anti-inflammatory Antigens Atrophic Autoimmune Process Autoimmunity Benign Prostatic Hypertrophy Binding Chronic Chronic Prostatitis Code Data Development Disease Environment Epidemiology Epithelial Cells Genitourinary system Glutathione S-Transferase Growth Homeostasis Hyperplasia IL8 gene Immune response Incidence Individual Induced Mutation Inflammation Inflammatory Inflammatory Response Interferons Interleukin-10 Interleukin-6 Intervention Link Maintenance Malignant neoplasm of prostate Membrane Modeling Myelogenous Office Visits Oncogenes Ovalbumin Pelvic Pain Pharmaceutical Preparations Predisposition Process Proliferating Prostate Prostatic Prostatic Diseases Proteins Reactive Oxygen Species Regulation Ribonucleases Risk Role Suppressor-Effector T-Lymphocytes Symptoms T-Lymphocyte Tissues Transgenic Mice Transgenic Organisms Tumor Necrosis Factor-alpha United States National Institutes of Health Wild Type Mouse adenoma base chronic pelvic pain cytokine experience intraepithelial macrophage scavenger receptors men middle age mouse model novel prostatitis public health relevance response tool

项目摘要

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.

描述（由申请人提供）：前列腺的慢性非细菌炎症与多种前列腺疾病有关，包括慢性前列腺炎 - 遗传性骨盆疼痛综合征（CP-CPPS），良性前列腺增生性增生（BPH）和前列腺癌。 CP-CPP是影响任何年龄段男性的骨盆疼痛症状疾病，据估计有50％的男性在其一生中经历了这种疾病。根据美国国立卫生研究院的说法，前列腺炎占年轻和中年男性涉及泌尿生殖系统的所有办公访问的25％。同样，慢性非细菌炎症实际上总是存在于BPH组织中。 BPH中的慢性炎症过程与增生有关，可能与组织重塑有关，从而导致腺瘤形成。炎症也与前列腺癌有关。为了解决前列腺炎症的问题，开发了一种新型的基因修饰小鼠模型。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起始和调控有关的因素所需的工具。初步数据证明了该模型的效用，并确定了一些对炎症及其调节重要的因素。这些数据为假设启动前列腺炎症的假设提供了一个基础，该假说扩展到包括用多种前列腺抗原反应的T细胞。此外，炎症均由MDSC和TREG调节。为了解决这一假设，提出了三个具体目的：目标1。慢性自身免疫性前列腺炎症的启动和维持，目标2。髓样衍生的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。对拟议研究的追求将提供有关与前列腺炎症起始和控制有关的因素的新信息。公共卫生相关性：前列腺的慢性非细菌炎症与多种前列腺疾病有关，包括慢性前列腺炎 - 频率骨盆疼痛综合征，良性前列腺增生性增生和前列腺癌。炎症与前列腺癌之间的联系正在接受。因此，定义控制非细菌慢性前列腺炎症所必需的参数至关重要。