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.
Chronic pelvic pain is the hallmark of patients with chronic pelvic pain syndrome (CPPS), a category of prostatitis that is a significant source of morbidity in American men. The cause of CPPS is unknown and there is an urgent need for understanding the disease mechanism to drive targeted therapy. This project will utilize components of prostate commensal bacteria to develop gold nanoparticle based therapeutics to modulate immune response and ameliorate pelvic pain in CPPS.
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