1602 UP-REGULATION OF ANDROGEN RESPONSIVE GENES AND TGF-Β1 CASCADE GENES INDUCED BY PROSTATIC INFLAMMATION

Abstract

You have accessJournal of UrologyBenign Prostatic Hyperplasia: Basic Research1 Apr 20131602 UP-REGULATION OF ANDROGEN RESPONSIVE GENES AND TGF-Β1 CASCADE GENES INDUCED BY PROSTATIC INFLAMMATION Yasuhito Funahashi, Zhou Wang, Katherine J O'Malley, Ryosuke Takahashi, Momokazu Gotoh, and Naoki Yoshimura Yasuhito FunahashiYasuhito Funahashi Nagoya, Japan More articles by this author , Zhou WangZhou Wang Pittsburgh, PA More articles by this author , Katherine J O'MalleyKatherine J O'Malley Pittsburgh, PA More articles by this author , Ryosuke TakahashiRyosuke Takahashi Pittsburgh, PA More articles by this author , Momokazu GotohMomokazu Gotoh Nagoya, Japan More articles by this author , and Naoki YoshimuraNaoki Yoshimura Pittsburgh, PA More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.3152AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Prostatic inflammation is reportedly associated with symptomatic BPH. We investigated the effects of prostatic inflammation on expression levels of androgen responsive genes and TGF-β1 cascade genes in the rat prostate. METHODS Prostatic inflammation was induced by either formalin injection into the ventral lobes of the prostate or E. coli injection into the prostatic urethra of male SD rats. Some rats were given a COX-2 inhibitor (celecoxib, 10 mg/kg/day) by oral gavage for 28 days prior to tissue examination. At 28 days after formalin injection or at 3 months after E.coli inoculation, ventral lobes of the prostate were excised, and histopathology (H&E staining and immunohistochemistry) and ELISA for pro-inflammatory cytokines were performed. Using laser-capture microdissection (LCM), glandular epithelial cells and stromal regions in the low-grade inflammatory regions were isolated separately, followed by real-time RT-PCR to examine mRNA levels of androgen-responsive genes and TGF-β1 cascade genes. RESULTS (1) Histopathology: The formalin-injected prostate exhibited widespread low-grade inflammation with high-grade inflammation in limited regions. In the E.coli-treated prostate, low-grade inflammation distributed diffusely. Positive staining for androgen receptor in the epithelial nuclei, TGF-β1, IL-6 and COX-2 in the stroma was up-regulated in the low-grade inflammation area of both groups. These up-regulations were suppressed in celecoxib-treated rats. (2) Cytokine levels: IL-1α, IL-1β, and IL-6 protein level were increased by 2.5-4 folds in the formalin-injected prostate and by 3-12 folds in the E.coli-injected prostate. These were suppressed by celecoxib administration. (3) LCM: Androgen receptors and androgen responsive genes such as Eaf2, ELL2, FKBP5, calreticulin and orinthine decarboxylase were up-regulated by 2-9 folds in the epithelial cells from the low-grade inflammatory regions. Androgen receptor and TGF-β1 cascade genes such as TGF-β1, Hic-5, and fibronectin were up-regulated by 2.5-15 folds in the stroma. These up-regulations were also suppressed in celecoxib-treated rats. CONCLUSIONS Prostatic inflammation increases expression of androgen responsive genes in the epithelium and TGF-β1 cascade genes in the stroma, suggesting that activation of these genes in the inflammatory area might be involved in the development of symptomatic BPH. Also, because COX-2 inhibition reduced up-regulation of these genes as well as prostatic inflammation, COX-2 inhibitors could be effective to suppress the BPH development. © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e658 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Yasuhito Funahashi Nagoya, Japan More articles by this author Zhou Wang Pittsburgh, PA More articles by this author Katherine J O'Malley Pittsburgh, PA More articles by this author Ryosuke Takahashi Pittsburgh, PA More articles by this author Momokazu Gotoh Nagoya, Japan More articles by this author Naoki Yoshimura Pittsburgh, PA More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...