W. Chronic bacterial infection and inflammation incite reactive hyperplasia in a mouse model of chronic prostatitis
ABSTRACT Chronic inflammation is postulated to contribute to prostate carcinogenesis. We developed a mouse model of chronic prostatitis to test whether infection-induced chronic inflammation would incite reactive changes in prostatic epithelium.
Prostate tissues harvested from either phosphate-buffered saline (PBS) or E. coli-infected mice were evaluated for histological changes and immunostained for markers of oxidative stress and epithelial cell proliferation.
As compared to PBS-treated controls, mice infected with E. coli bacteria for 5 days showed foci of uniformly acute inflammation in the glandular lumen and a persistent inflammation at 12 weeks post-inoculation in the stroma. Prostatic glands showing varying degrees of atypical hyperplasia and dysplasia had stronger staining for oxidative DNA damage and increased epithelial cell proliferation than normal prostatic glands.
These data demonstrate that chronic inflammation induces reactive hyperplasia associated with oxidative stress injury and support the proposed linkage among inflammation, oxidative DNA damage, and prostate carcinogenesis.
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- "However, a causal relationship between inflammation and fibrosis of the prostate has never been established. The purpose of this study was to examine directly whether inflammation causes fibrosis in a previously described mouse model of bacterial-induced prostatic inflammation , . While there are significant species-specific differences in the anatomy, cellular and extracellular matrix compositions in the stroma of the mouse and human prostate , , the stromal-epithelial interactions are highly conserved between them  and the inflammatory responses to bacterial infection in the mouse prostate, in particular, appears to recapitulate the immunologic features of inflammation in the human prostate , –. "
ABSTRACT: Inflammation of the prostate is strongly correlated with development of lower urinary tract symptoms and several studies have implicated prostatic fibrosis in the pathogenesis of bladder outlet obstruction. It has been postulated that inflammation induces prostatic fibrosis but this relationship has never been tested. Here, we characterized the fibrotic response to inflammation in a mouse model of chronic bacterial-induced prostatic inflammation. Transurethral instillation of the uropathogenic E. coli into C3H/HeOuJ male mice induced persistent prostatic inflammation followed by a significant increase in collagen deposition and hydroxyproline content. This fibrotic response to inflammation was accompanied with an increase in collagen synthesis determined by the incorporation of 3H-hydroxyproline and mRNA expression of several collagen remodeling-associated genes, including Col1a1, Col1a2, Col3a1, Mmp2, Mmp9, and Lox. Correlation analysis revealed a positive correlation of inflammation severity with collagen deposition and immunohistochemical staining revealed that CD45+VIM+ fibrocytes were abundant in inflamed prostates at the time point coinciding with increased collagen synthesis. Furthermore, flow cytometric analysis demonstrated an increased percentage of these CD45+VIM+ fibrocytes among collagen type I expressing cells. These data show-for the first time-that chronic prostatic inflammation induces collagen deposition and implicates fibrocytes in the fibrotic process.PLoS ONE 06/2014; 9(6):e100770. DOI:10.1371/journal.pone.0100770 · 3.23 Impact Factor