MP19-19 INTERLEUKIN-18 MAY LEAD TO STOROMAL HYPERPLASIA VIA THROMBOSPONDIN-1 PRODUCTION IN PROSTATIC SMOOTH MUSCLE CELLS.

Abstract

You have accessJournal of UrologyBenign Prostatic Hyperplasia: Basic Research1 Apr 2014MP19-19 INTERLEUKIN-18 MAY LEAD TO STOROMAL HYPERPLASIA VIA THROMBOSPONDIN-1 PRODUCTION IN PROSTATIC SMOOTH MUSCLE CELLS. Takashi Hamakawa, Shoichi Sasaki, Yasue Kubota, Yoshiyuki Kojima, and Kenjiro Khori Takashi HamakawaTakashi Hamakawa More articles by this author , Shoichi SasakiShoichi Sasaki More articles by this author , Yasue KubotaYasue Kubota More articles by this author , Yoshiyuki KojimaYoshiyuki Kojima More articles by this author , and Kenjiro KhoriKenjiro Khori More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2014.02.720AboutPDF 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. To investigate the gene and protein of IL-18 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. Furthermore, to analyze the effect of TSP-1 and IL-18 on cell proliferation, we carried out WST assay on prostate smooth muscle cells (PrSMC) and stromal cells (PrSC). RESULTS 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. In cell proliferation assay, IL-18 did not effect cell proliferation of PrSMC and PrSC. Other hands, TSP-1 promoted cell proliferation of PrSC. CONCLUSIONS IL-18 stimulates TSP-1 production from prostatic SMCs. TSP-1 induces stromal cells proliferation and may leads to the development of stromal 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. © 2014FiguresReferencesRelatedDetails Volume 191Issue 4SApril 2014Page: e195-e196 Advertisement Copyright & Permissions© 2014MetricsAuthor Information Takashi Hamakawa More articles by this author Shoichi Sasaki More articles by this author Yasue Kubota More articles by this author Yoshiyuki Kojima More articles by this author Kenjiro Khori More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...