Premium
Interleukin‐18 may lead to benign prostatic hyperplasia via thrombospondin‐1 production in prostatic smooth muscle cells
Author(s) -
Hamakawa Takashi,
Sasaki Shoichi,
Shibata Yasuhiro,
Imura Makoto,
Kubota Yasue,
Kojima Yoshiyuki,
Kohri Kenjiro
Publication year - 2014
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.22773
Subject(s) - stromal cell , hyperplasia , prostate , thrombospondin 1 , pathogenesis , cytokine , cancer research , immunostaining , inflammation , benign prostatic hyperplasia (bph) , biology , medicine , endocrinology , immunohistochemistry , angiogenesis , cancer
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. Prostate 74:590–601, 2014. © 2014 Wiley Periodicals, Inc.