1597 INTERLEUKIN-18 MAY LEAD TO BENIGN PROSTATIC HYPERPLASIA VIA THROMBOSPONDIN-1 PRODUCTION IN PROSTATIC SMOOTH MUSCLE CELLS

Abstract

You have accessJournal of UrologyBenign Prostatic Hyperplasia: Basic Research1 Apr 20131597 INTERLEUKIN-18 MAY LEAD TO BENIGN PROSTATIC HYPERPLASIA VIA THROMBOSPONDIN-1 PRODUCTION IN PROSTATIC SMOOTH MUSCLE CELLS Takashi Hamakawa, Shoichi Sasaki, Yasuhiro Shibata, Makoto Imura, Yasue Kubota, Yoshiyuki Kojima, and Kenjiro Kohri Takashi HamakawaTakashi Hamakawa Nagoya, Japan More articles by this author , Shoichi SasakiShoichi Sasaki Nagoya, Japan More articles by this author , Yasuhiro ShibataYasuhiro Shibata Nagoya, Japan More articles by this author , Makoto ImuraMakoto Imura Nagoya, Japan More articles by this author , Yasue KubotaYasue Kubota Nagoya, Japan More articles by this author , Yoshiyuki KojimaYoshiyuki Kojima Fukushima, Japan More articles by this author , and Kenjiro KohriKenjiro Kohri Nagoya, Japan More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.3147AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Inflammation plays an important role in the development of benign prostatic hyperplasia (BPH), but little is known about the exact mechanism of pathogenesis. To elucidate the relationship between the inflammatory reaction and development of BPH, we established a stromal hyperplasia rat model and analyzed the genomic profile of this model by using cDNA microarray. We focused on the most expressed pro-inflammatory cytokine IL-18 in several genes related to the inflammatory response. The aim of the present study was to clearly understand the relationship between the development of BPH and IL-18. METHODS We produced an experimental BPH rat model with pathologically stromal component-dominant hyperplasia. The fetal urogenital sinus (UGS) was dissected from 20-day-old rats and the UGS were transplanted into the right ventral prostate of 7-week-old SD rats. After 21 days, the host rats were sacrificed. The ventral prostate of host rats was dissected and used as samples. cDNA microarray analysis was used to identify changes in inflammation-related gene expression in a BPH rat model. To investigate the genes and proteins identified in the analysis, quantitative (q)RT-PCR, western blotting, and immunostaining were conducted using BPH model tissues, human prostate tissues, and prostate smooth muscle cells (PrSMCs). RESULTS Of 31,100 genes identified in the cDNA analysis, 7 genes related to the inflammatory response were expressed at a >2-fold higher level in rat BPH tissues than normal prostate tissues. IL-18 was the highest expression among the inflammatory cytokines in this analysis. IL-18 expression was significantly increased in rat BPH tissues, and IL-18 localized in the epithelial and stromal components, while its receptor strongly localized in smooth muscle cells in human prostate tissues. IL-18 treatment of PrSMCs induced a dose-dependent increase in phosphorylated Akt expression, but no change was noted in Akt. Further, thrombospondin-1 (TSP-1), an activator of TGFb, production by PrSMC increased in a dose-dependent manner with IL-18 treatment. CONCLUSIONS IL-18 stimulates TSP-1 production from prostatic SMCs. TGF-β activated by TSP-1 induces the differentiation of prostatic stromal cell, which in turn leads to the development of prostatic hyperplasia. Thus, our findings indicate that IL-18 may act directly in the pathogenesis of BPH by inducing TSP-1 production from SMCs via Akt phosphorylation. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e656 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Takashi Hamakawa Nagoya, Japan More articles by this author Shoichi Sasaki Nagoya, Japan More articles by this author Yasuhiro Shibata Nagoya, Japan More articles by this author Makoto Imura Nagoya, Japan More articles by this author Yasue Kubota Nagoya, Japan More articles by this author Yoshiyuki Kojima Fukushima, Japan More articles by this author Kenjiro Kohri Nagoya, Japan More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...