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.

Public Health Relevance

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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK108127-02
Application #
9315811
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Kirkali, Ziya
Project Start
2016-08-01
Project End
2020-07-31
Budget Start
2017-08-01
Budget End
2018-07-31
Support Year
2
Fiscal Year
2017
Total Cost
Indirect Cost
Name
Northwestern University at Chicago
Department
Urology
Type
Schools of Medicine
DUNS #
005436803
City
Chicago
State
IL
Country
United States
Zip Code
60611