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.
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: Amparo Urios; Felipe Ordoño; Raquel García-García; Alba Mangas-Losada; Paola Leone; Juan José Gallego; Andrea Cabrera-Pastor; Javier Megías; Juan Fermin Ordoño; Vicente Felipo; Carmina Montoliu Journal: Sci Rep Date: 2019-11-19 Impact factor: 4.379