The Expression And Function Of Interleukin 21 Receptor In Benign Prostatic Hyperplasia

Background Benign prostatic hyperplasia(BPH)is a common urological disease in aging men.But the pathophysiology remains unclear.Many interleukins(ILs)and related chronic inflammatory markers have been found to contribute to the development of BPH.As a late member of ILs family,IL-21 receptor(IL-21R)can modulate cell proliferation,however,IL-21 R activity in the prostate has not been examined.The current study aimed to elucidate a potential role of IL-21 R in the development of BPH.Material and methods In this study,human prostate tissues,prostate cell lines and rats were used.The expression and localization of IL-21 R were determined with quantitative real-time PCR,Western Blot,and immunohistochemistry staining in human prostate tissues.BPH-1 cells with IL-21 R silenced were cultured or co-cultured with macrophages(active THP-1,AcTHP-1).Apoptosis and cell cycles were tested with Flow Cytometry and Western Blot.Epithelial-mesenchymal transition(EMT)processes were detected with Western Blot and immunofluorescent staining.In vivo,rat prostatitis concomitant with BPH model was induced through intraprostatic injection of lipopolysaccharide(LPS).Rat prostate was observed with Hematoxylin and Eosin(HE)staining and masson’s trichrome staining.The expression,localization and functional activities of IL-21 R in rat prostate were also examined.Results IL-21 R was found to be highly expressed in human,as well as rat,prostate,mainly in the epithelial compartment.BPH concomitant with prostatitis significantly upregulated the expression of IL-21 R.Knockdown of IL-21 R induced cell apoptosis and cycle arrest at G0/G1 phase,and blocked EMT processes in BPH-1 cells.When IL-21 R silenced BPH-1 cells were co-cultured with AcTHP-1 cells,these aforementioned processes and IL-21 R change were completely reversed.Prostatic hyperplasia was observed with IL-21 R upregulated in LPS induced prostatitis rats.The expression of apoptosis,cyclin,and EMT proteins in this rat model are altered in a manner consistent with that seen in the cell line model.Conclusions Our novel data demonstrates the expression and functional activities of IL-21 R in the mechanism for development of BPH.IL-21 R mainly localized in prostate epithelium and it was upregulated in hyperplastic prostate tissues.IL-21 R enhanced proliferation of BPH-1 cells,via inhibiting cell apoptosis,and modulating cell cycles,as well as the EMT process,in response to inflammatory stimuli.