Urology, University of Wisconsin - Madison

Mouse Model of Chronic Prostate Inflammation

Funding:

National Institutes of Health

Principal Investigator:

Wade Bushman, MD

Lab Website:

Dr. Bushman's Lab

Project Summary:

Acute and chronic inflammations are an extremely common histopathologic finding in the human prostate. The origin of inflammation in the prostate remains a subject of debate and may in fact be multi-factorial, but there is evidence that bacterial colonization of the human prostate occurs frequently and evidence that prostatic inflammation is often associated with the presence of bacteria. Further, the coincidence of chronic inflammation and tumorigenesis in the peripheral zone has recently been linked by studies identifying so- called proliferative inflammatory atrophy (PIA) as a possible precursor of prostatic intraepithelial neoplasia (PIN) and prostate cancer (CaP). These findings highlight the need for a well described mouse model to examine and study the effects of chronic bacterial inflammation on the prostate and to determine the potential for such inflammation to incite reactive epithelial proliferation and to create conditions that are conducive to reactive dysplasia and neoplasia. We have conducted preliminary studies showing that C3H/HeOuJ inbred male mice inoculated intraurethrally with uropathogenic E. coli develop significant prostate infections and have preliminary data showing that prolonged infection and inflammation result in a reactive hyperplasia which progresses over time to hyperplasia associated with severe dysplasia. This proposal addresses the hypothesis that chronic bacterial infection of the prostate produces chronic prostatic inflammation and reactive epithelial hyperplasia. We will test this hypothesis by developing a novel, well defined mouse model of chronic bacterial prostatitis and using it to characterize the inflammatory response to bacterial infection and the effect of chronic inflammation on the prostate epithelium. Three specific aims of this proposal are: 1. To define the inoculum dose of uropathogenic E. coli necessary to reliably produce prostatic infection and to examine the relationship of inoculum to the duration of infection and the magnitude of the inflammatory response. 2. To characterize the acute and chronic bacterial inflammatory response to infection by quantitating inflammatory cell infiltrate and the expression of inflammatory mediators 3. To characterize the effect of chronic infection and inflammation on epithelial proliferation and apoptosis and to characterize in detail the reactive hyperplasia and dysplasia that appears during chronic inflammation.

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