title: Interleukin-18 may lead to benign prostatic hyperplasia via thrombospondin-1 production in prostatic smooth muscle cells.
abstract: BACKGROUND
  Although inflammation plays an important role in the development of benign prostatic hyperplasia (BPH), little is known about the exact mechanism underlying this pathogenesis. Here, we investigated the relationship between the inflammatory reaction and BPH.
  
  
  METHODS
  cDNA microarray analysis was used to identify changes in inflammation-related gene expression in a recently established rat model that mimics human BPH. To investigate the genes identified in the analysis, quantitative (q)RT-PCR, Western blotting, immunostaining, and a cell proliferation assay were conducted using BPH model tissues, human prostate tissues, and normal human prostate cultured cells.
  
  
  RESULTS
  Of the 31,100 genes identified in the cDNA analysis, seven inflammatory-response-related genes were expressed at a >2-fold higher level in rat BPH tissues than in normal rat prostate tissues. The levels of the most commonly expressed pro-inflammatory cytokine, IL-18, significantly increased in rat BPH tissues. In humans, IL-18 was localized in the epithelial and stromal components, while its receptor was strongly localized in smooth muscle cells. Furthermore, in human prostate smooth muscle cell line (PrSMC), IL-18 effected dose-dependent increases in the phosphorylated Akt and thrombospondin-1 (TSP-1) levels. TSP-1 promoted proliferation of the human prostate stromal cells (PrSC).
  
  
  CONCLUSIONS
  IL-18 may act directly in BPH pathogenesis by inducing TSP-1 production in prostatic smooth muscle cells via Akt phosphorylation.
authors.affiliation: Department of Nephro-Urology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Hamakawa
authors.forename: Shoichi
authors.initials: S
authors.lastname: Sasaki
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Shibata
authors.forename: Makoto
authors.initials: M
authors.lastname: Imura
authors.forename: Yasue
authors.initials: Y
authors.lastname: Kubota
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Kojima
authors.forename: Kenjiro
authors.initials: K
authors.lastname: Kohri
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002478:Cells, Cultured; D004195:Disease Models, Animal; D006801:Humans; D020382:Interleukin-18 / Q000235:genetics / Q000378:metabolism*; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D011467:Prostate / Q000378:metabolism* / Q000473:pathology; D011470:Prostatic Hyperplasia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology; D019700:Thrombospondin 1 / Q000235:genetics / Q000378:metabolism*
chemical_list: D020382:Interleukin-18; D019700:Thrombospondin 1; D051057:Proto-Oncogene Proteins c-akt
keywords: IL-18; TSP-1; benign prostatic hyperplasia; inflammation