Upregulation ofAndrogen- ResponsiveGenes and TransformingGrowth Factor-b1CascadeGenes in a Rat Model of Non-Bacterial Prostatic Inflammation

BACKGROUND Prostatic inflammation is 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 prostate. METHODSProstatic inflammation was induced by formalin injection into bilateral ventral lobes of the prostate of male SD rats. After 28 days, the prostate was harvested for analyses of proinflammatory cytokines, androgen-responsive genes in the epithelium, and TGF-1 cascade genes in the stroma. Some rats were given a COX-2 inhibitor (celecoxib; 10mg/kg/day) by oral gavage for 28 days. RESULTSThe formalin-injected prostate exhibited widespread low-grade inflammation (<50leukocytes/10,000m(2)) along with focal high-grade inflammation (>100leukocytes/10,000m(2)) in limited areas. Compared to control, formalin-injected prostate exhibited a 2.5-fold to sixfold increased protein expression of IL-1, IL-1, and IL-6. In the low-grade inflammatory regions, threefold to ninefold and twofold to threefold upregulations of mRNA levels of androgen receptors/androgen-responsive genes and TGF-1 cascade genes were respectively, observed in the epithelium and stroma obtained by laser-capture microdissection. Positive staining for androgen receptors in the epithelial nuclei, and TGF-1, IL-6, and COX-2 in the stroma was increased in the low-grade inflammation area. COX-2 inhibitor treatment suppressed these upregulations of cytokines, androgen-responsive, and TGF-1 cascade genes. CONCLUSIONSProstatic inflammation induced increased expression of androgen-responsive genes in the epithelium and TGF-1 cascade genes in the stroma, which were suppressed by COX-2 inhibitors, suggesting that activation of these genes in the low-grade inflammatory region might be involved in the development of symptomatic BPH. Prostate 74:337-345, 2014. (c) 2013 Wiley Periodicals, Inc.