PD33-11 CD3+ T CELLS SUPPRESS ANDROGEN RECEPTOR IN BPH VIA IL-1β/MIR-15B-5P SIGNALING TO AFFECT 5 ALPHA REDUCTASE INHIBITOR TREATMENT

Abstract

You have accessJournal of UrologyBenign Prostatic Hyperplasia: Medical & Non-surgical Therapy (PD33)1 Apr 2020PD33-11 CD3+ T CELLS SUPPRESS ANDROGEN RECEPTOR IN BPH VIA IL-1β/MIR-15B-5P SIGNALING TO AFFECT 5 ALPHA REDUCTASE INHIBITOR TREATMENT Hualin Song*, shuai hu, and Jie Jin Hualin Song*Hualin Song* More articles by this author , shuai hushuai hu More articles by this author , and Jie JinJie Jin More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000904.011AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: 5 alpha reductase inhibitor (5ARI) is widely used in the treatment of benign prostatic hyperplasia (BPH), and has achieved good therapeutic effects, but 30%-40% of patients still have poor therapeutic effect, and subsequent surgery is needed. We found that patients with poor 5ARI treatment had more infiltration of CD3+ T cells than patients with good treatment. At the same time, we found that the expression of androgen receptor (AR) in the infiltrated area of CD3+ T cells in human BPH specimen epithelial cells was reduced. However, the regulatory relationship between these two events remains unclear. The aim of this study was to investigate whether CD3+ T cells can regulate AR expression and whether it can affect the therapeutic effects of 5ARI. METHODS: Paraffin-embedded tissues obtained from TURP were used for expression of CD3 and AR protein by IHC. RWPE-1, BPH-1-AR cells (transfect AR into BPH-1 cells) and PWR-1E cells were co-cultured with/without CD3+ T cells-Molt-3 and HH cells. AR expression in BPH epithelial cells after co-cultured were detected by Western blot. Cytokines in co-cultured supernatant were detected by cytokines array and qPCR. The high-throughput sequencing was used to detect miRNAs expression in RWPE-1 and BPH-1-AR cells after co-cultured. RESULTS: Patients with poor 5ARI treatment had more infiltration of CD3+ T cells than patients with good treatment. Expression of AR in epithelial cells was reduced in the area of CD3+ T cells infiltration in clinical samples. AR expression was also significantly reduced in BPH epithelial cells after co-cultured with CD3+ T cells. IL-1β was increased in co-cultured supernatant and it was secreted by CD3+T cells. Meanwhile, miRNA-15b-5p was also significantly increased in BPH epithelial cells after co-cultured. Mechanism dissection revealed that infiltrating CD3+ T cells secreted IL-1β to up-regulate miRNA-15b-5p in BPH epithelial cells to suppress AR. Targeting these newly identified signals via IL-1β neutralizing antibody or miRNA-15b-5p inhibitor both led to partially reverse the AR reduction. CONCLUSIONS: This study was concluded that infiltrating CD3+ T cells could suppress AR to in BPH via modulation of IL-1β/miR-15b-5p signaling. The AR level that has been reduced makes the effect of 5ARI no longer obvious, which is one of the reasons for patients with poor 5ARI treatment. Targeting these newly discovered signals and 5ARI combination may improve treatment outcomes to better treat patients with BPH. Source of Funding: None. © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e709-e710 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Hualin Song* More articles by this author shuai hu More articles by this author Jie Jin More articles by this author Expand All Advertisement PDF downloadLoading ...