Lipoteichoic acid mediated immune modulation of chronic pain

脂磷壁酸介导的慢性疼痛的免疫调节

• 批准号: 9177358
• 负责人: PRAVEEN THUMBIKAT
• 金额: $ 35.19万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-08-01 至 2020-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9177358
• 关键词: Accounting; American; Anogenital region; Antigen-Presenting Cells; Antigens; Attenuated; Autoimmune Process; Bacteria; Biological Assay; Bone Marrow; CD4 Positive T Lymphocytes; Calcium Signaling; Categories; Cell Wall; Cells; Characteristics; Chronic; Chronic Prostatitis; Clinical; Coupled; Development; Diagnosis; Disease; Dysuria; Escherichia coli; Etiology; Future; Gold; HDL receptor; High Density Lipoproteins; Human; Human Volunteers; IL2RA gene; Immune; Immune response; Immunity; Immunosuppression; In Vitro; Infection; Injury; Interleukin-10; Intestines; Lead; Life; Ligands; Mediating; Mediator of activation protein; Modeling; Molecular; Morbidity - disease rate; Mus; Names; Nature; Neural Pathways; Neurons; Nociception; Outpatients; PDCD1LG1 gene; Pain; Parents; Patients; Pelvic Pain; Peripheral Blood Mononuclear Cell; Primary Care Physician; Prostate; Regulatory T-Lymphocyte; Reporting; Role; Self Tolerance; Signal Transduction; Source; Staphylococcus epidermidis; Syndrome; T-Lymphocyte; TLR2 gene; Testing; Testis; Therapeutic; United States; Visit; attenuation; base; chronic pain; chronic pelvic pain; commensal microbes; immune activation; immunoregulation; in vitro testing; in vivo; lipoteichoic acid; macrophage; mast cell; men; microbial; monocyte; mouse model; nanoparticle; novel; pathogen; penis; prostatitis; reconstitution; response; scavenger receptor; targeted treatment

Summary Prostatitis accounts for 2 million outpatient visits per year in the United States, including 1% of those to primary care physicians. Chronic pelvic pain syndrome (CPPS) is clinically characterized by dysuria and pain in the perineum, testes, penis and suprapubic region. CPPS accounts for 90% of all chronic prostatitis but the initiating factors that establish the syndrome are unknown. We hypothesized that bacterial isolates from the prostate, particularly long--‐lived clinical strains and resident commensals, are capable of influencing prostate immunity. When mice with non--‐infectious autoimmune prostatitis (Experimental autoimmune prostatitis - EAP), were instilled with the commensal S. epidermidis, there was a rapid amelioration of pelvic pain and a negative modulation of the pathogenic immune response in the prostate. These results lead us to hypothesize that S. epidermidis LTA (SELTA) induces expression of co--‐stimulatory ligands to inhibit effector T cells, activate regulatory T cells and abrogate mast cell degranulation, resulting in the amelioration of pelvic pain. We therefore propose the following specific aims: 1. Identifying the mechanism of pain attenuation mediated by S. epidermidis LTA. 2. Defining the role of TLR’s in SELTA--‐mediated immune modulation. 3. Evaluating SELTA conjugatedHDL--‐goldnanoparticles as a therapeutic for pelvic pain. The proposed studies will provide a mechanistic understanding of how SELTA inhibits pelvic pain and will develop novel cutting--‐edge therapeutics for testing in human CP/CPPS.

总结 在美国，前列腺炎每年占200万门诊就诊人数，其中包括1%的原发性前列腺炎患者。 护理医生慢性骨盆疼痛综合征（CPPS）的临床特征是排尿困难和疼痛， 会阴、睾丸、阴茎和耻骨上区域。CPPS占所有慢性前列腺炎的90%， 引起该综合征的因素尚不清楚。我们假设， 前列腺，特别是长期存活的临床菌株和常驻菌株，能够影响前列腺 免疫力当患有非感染性自身免疫性前列腺炎（实验性自身免疫性前列腺炎- EAP），滴注了Escherosal S。表皮，盆腔疼痛迅速改善， 前列腺中致病性免疫应答的负调节。这些结果让我们假设 那辆多表皮LTA（SELTA）诱导共刺激配体的表达以抑制效应T细胞， 激活调节性T细胞并消除肥大细胞脱粒，从而改善盆腔疼痛。我们 为此提出以下具体目标：1.确定S. 表皮2.定义TLR在SELTA介导的免疫调节中的作用。3.评价SELTA 结合高密度脂蛋白-金纳米颗粒作为盆腔疼痛的治疗剂。拟议的研究将提供一个 了解SELTA如何抑制骨盆疼痛的机制，并将开发新的切割-边缘 用于在人CP/CPPS中测试的治疗剂。