title: Influence of E. coli-induced prostatic inflammation on expression of androgen-responsive genes and transforming growth factor beta 1 cascade genes in rats.
abstract: BACKGROUND
  Prostatic inflammation is reportedly associated with the development of prostatic hyperplasia. We investigated the effects of prostatic inflammation on expression levels of androgen-responsive genes and growth factors in the rat prostate.
  
  
  METHODS
  Prostatic inflammation was induced by Escherichia coli (strain 1677) injection (0.2 ml of 1 × 10(8) CFU/ml) into the prostatic urethra of male Sprague-Dawley rats, and ventral lobes of the prostate were harvested on day 84. Rats were given 10 mg/kg celecoxib during the last month in the COX-2 inhibitor treated group. Histopathology and multiplex enzyme-linked immunosorbent assay (ELISA) for inflammation-related proteins were performed. Glandular epithelial cells and stromal regions were separately isolated using laser-capture microdissection (LCM). Real-time RT-PCR was performed to examine mRNA levels of androgen-responsive genes in the epithelium and tumor growth factor-β1 (TGF-β1) cascade genes in the stroma.
  
  
  RESULTS
  Hematoxylin and eosin staining showed that mild inflammation was distributed diffusely throughout the prostate. Polymorphonuclear cells infiltrated the slightly edematous stroma, but no morphological changes were observed in the epithelium. Immunohistochemically, expression of androgen receptor and TGF-β1 in addition to IL-6 and cyclooxigenase-2 (COX-2) were enhanced in the E. coli inoculated rats. All of these factors were suppressed in the celecoxib-treated rats. Upregulation of IL-1α, IL-1β, IL-6, and RANTES in the E. coli-inoculated rats was normalized by celecoxib treatment. Significant upregulation of androgen receptor and androgen-responsive genes such as Eaf2, ELL2, FKBP5, calreticulin, and ornithine decarboxylase was observed in the LCM-dissected epithelium. Also TGF-β1 and its downstream cascade genes such as Hic-5, collagen 1, and fibronectin were upregulated significantly in the LCM-dissected stroma. The COX-2 inhibitor treatment suppressed upregulation of these genes.
  
  
  CONCLUSIONS
  Prostatic inflammation changed the expression of androgen-responsive genes in the epithelium and TGF-β1 cascade genes in the stroma. Activation of TGF-β1 cascade genes in the inflamed stroma, as well as altered androgen-responsive gene expression in the epithelium, might be involved in the development of BPH. Prostate 75:381-389, 2015. © 2014 Wiley Periodicals, Inc.
authors.affiliation: Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania; Department of Urology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Funahashi
authors.forename: Zhou
authors.initials: Z
authors.lastname: Wang
authors.forename: Katherine J
authors.initials: KJ
authors.lastname: O'Malley
authors.forename: Pradeep
authors.initials: P
authors.lastname: Tyagi
authors.forename: Donald B
authors.initials: DB
authors.lastname: DeFranco
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Gingrich
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Takahashi
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Majima
authors.forename: Momokazu
authors.initials: M
authors.lastname: Gotoh
authors.forename: Naoki
authors.initials: N
authors.lastname: Yoshimura
mesh_terms: D000728:Androgens; D000818:Animals; D045744:Cell Line, Tumor; D004926:Escherichia coli; D007378:Interleukins / Q000378:metabolism; D008297:Male; D011470:Prostatic Hyperplasia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011472:Prostatitis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D000728:Androgens; D007378:Interleukins; D011944:Receptors, Androgen; D053773:Transforming Growth Factor beta1
keywords: TGF-β1; androgen receptor; inflammation; laser capture microdissection; prostate