New therapy with ASC-J9® to suppress the prostatitis via altering the cytokine CCL2 signals.

Shin-Jen Lin,Hong-Chiang Chang,Fu-Ju Chou,Chang-Yi Lin,Shuyuan Yeh,Chawnshang Chang

doi:10.18632/oncotarget.11484

Shin-Jen Lin, Hong-Chiang Chang + Show 4 more

Open Access

https://doi.org/10.18632/oncotarget.11484

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Journal: Oncotarget	Publication Date: Aug 22, 2016
Citations: 6	License type: cc-by

Affiliation: University of Rochester Medical Center

Abstract

Prostatitis is a common disease contributing to 8% of all urologist visits. Yet the etiology and effective treatment remain to be further elucidated. Using a non-obese diabetes mouse model that can be induced by autoimmune response for the spontaneous development of prostatitis, we found that injection of the ASC-J9® at 75 mg/Kg body weight/48 hours led to significantly suppressed prostatitis that was accompanied with reduction of lymphocyte infiltration with reduced CD4+ T cells in prostate. In vitro studies with a co-culture system also confirmed that ASC-J9® treatment could suppress the CD4+ T cell migration to prostate stromal cells. Mechanisms dissection indicated that ASC-J9® can suppress CD4+ T cell migration via decreasing the cytokine CCL2 in vitro and in vivo, and restoring CCL2 could interrupt the ASC-J9® suppressed CD4+ T cell migration. Together, results from in vivo and in vitro studies suggest that ASC-J9® can suppress prostatitis by altering the autoimmune response induced by CD4+ T cell recruitment, and using ASC-J9® may help us to develop a potential new therapy to battle the prostatitis with little side effects.

Highlights

Prostatitis is characterized with inflammations in the prostate gland that are classified into acute, chronic, asymptomatic inflammatory prostatitis and chronic pelvic pain syndrome
Using a nonobese diabetes mouse model that can be induced by autoimmune response for the spontaneous development of prostatitis, we found that injection of the ASC-J9® at 75 mg/Kg body weight/48 hours led to significantly suppressed prostatitis that was accompanied with reduction of lymphocyte infiltration with reduced CD4+ T cells in prostate
We demonstrated that infiltrated CD4+ T cells play important roles in prostatitis by using NOD mice which can be rescued by ASC-J9®, the newly developed androgen receptor (AR) degradation enhancer

Summary

Introduction

Prostatitis is characterized with inflammations in the prostate gland that are classified into acute, chronic, asymptomatic inflammatory prostatitis and chronic pelvic pain syndrome. There are four categories of prostatitis [2]: category I includes acute bacterial prostatitis; category II includes chronic bacterial prostatitis, category III includes chronic prostatitis/ chronic pelvic pain syndrome (CP/CPPS); and category IV includes asymptomatic inflammatory prostatitis. CP/CPPS accounts for 90%–95% of prostatitis diagnoses [3]. The etiology of this type of prostatitis is still poorly understood. It may result from an interplay between psychological factors and dysfunction in the immune, neurological and endocrine systems [4]. An autoimmune basis for CP/CPPS is a prominent theory for the etiology/pathogenesis of CP/CPPS [5]. Animal models, named as experimental autoimmune prostatitis [6], with the characteristic of CD4-positive T cell infiltrates, have been used as standard in vivo models to study the progress of prostatitis

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