MP44-10 CD8+ T CELLS PROMOTE PROLIFERATION OF BENIGN PROSTATIC HYPERPLASIA EPITHELIAL CELLS IN THE CONDITION OF LOW ANDROGEN VIA MODULATION OF CCL5 -> STAT5 -> CYCLIN D1 SIGNALING

You have accessJournal of UrologyBenign Prostatic Hyperplasia: Basic Research & Pathophysiology1 Apr 2016MP44-10 CD8+ T CELLS PROMOTE PROLIFERATION OF BENIGN PROSTATIC HYPERPLASIA EPITHELIAL CELLS IN THE CONDITION OF LOW ANDROGEN VIA MODULATION OF CCL5 -> STAT5 -> CYCLIN D1 SIGNALING Yang Yang, Shuai Hu, Yun Cui, Yu Fan, Tianjing Lv, Qun He, Wei Yu, and Jie Jin Yang YangYang Yang More articles by this author , Shuai HuShuai Hu More articles by this author , Yun CuiYun Cui More articles by this author , Yu FanYu Fan More articles by this author , Tianjing LvTianjing Lv More articles by this author , Qun HeQun He More articles by this author , Wei YuWei Yu More articles by this author , and Jie JinJie Jin More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.266AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Previous studies of our group have shown that low intra-prostatic dihydrotestosterone (DHT) induced the BPH epithelial cells (BECs) to recruit CD8+ T cells via modulation of CCL5 secretion. Therefore, this study was intended to further evaluate the effect of CD8+ T cells on BECs in low DHT condition, and the mechanism was also investigated. METHODS Prostate tissues were obtained from 27 BPH patients with finasteride treatment underwent TURP. The expression of CD8, CCL5 and PCNA were analyzed by serial sections immunohistochemistry (IHC) to study the relationship among CD8+ T cells, CCL5 and proliferation of prostate epithelial cells. In vitro co-culture system, proliferation of Bph-1 cells with/without CD8+ T cell line--Molt-3 cells in low DHT condition (medium with charcoal FBS) was tested by CCK8 assay and the expression of PCNA was analyzed by western blot assay. After co-culture, Q-PCR was used to identify CCL5 expression in Bph-1 cells and Molt-3 cells. Finally, CCL5 neutralizing antibody were used for interruption assay to evaluate the proliferation effect of CD8+ T cells or rhCCL5 on BECs by CCK8 assay, and the activation of Stat5 and Cyclin D1 was also investigated by western blot assay in BECs. RESULTS By IHC study, compared to the area of less CD8+ T cells infiltrated, the PCNA and CCL5 expressions showed higher in the BECs where surrounding more CD8+ T cells infiltrated. In vitro data, the consequences of recruitment more CD8+ T cells to BECs in the low DHT condition could lead to enhanced BECs proliferation. Mechanism dissection revealed that co-culture of BECs with CD8+ T cells enhanced increasing chemokine CCL5 secretion which could result in activation of Stat5 --> Cyclin D1 signaling related to the cell-cycle for the promotion of BECs proliferation. Interruption approaches using neutralizing antibody reversed either the CD8+ T cells-enhanced or rhCCL5-enhanced BECs proliferation. CONCLUSIONS The present study showed that infiltrating CD8+ T cells could promote the proliferation of BECs in low androgen condition via modulation of CCL5 -> Stat5 -> Cyclin D1 signaling. The increased secretion of CCL5 come from CD8+ T cells/BECs interaction might help BECs to survive in the condition of low DHT. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e602 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Yang Yang More articles by this author Shuai Hu More articles by this author Yun Cui More articles by this author Yu Fan More articles by this author Tianjing Lv More articles by this author Qun He More articles by this author Wei Yu More articles by this author Jie Jin More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...