Acute bacterial inflammation of the mouse prostate

Abstract

BACKGROUND Prostatic inflammation is gaining increasing attention as a potential etiologic factor in prostate cancer, benign prostatic hyperplasia, lower urinary tract symptoms, and CPPS. This study was performed to address the need for a well characterized model of acute prostatic inflammation that may be used to study the effect of acute inflammation on epithelial and stromal cell proliferation, voiding behavior, and neurovascular physiology. METHODS Uropathogenic E. coli 1677 was instilled transurethrally into adult C57BL/6J male mice. Prostates were analyzed at 1, 2, 3, 5, 7, or 14 days post-instillation and compared to saline-instilled and naïve controls. Time course and severity of inflammation were characterized by the quantity and type of inflammatory infiltrate present, hemorrhage, proliferation, and reactive hyperplasia. RT-PCR was performed to characterize inflammatory mediators including IL-1α, IL-1β, IL-1RA, IL-18, IL-6, IL-10, IL-8, TNFα, and COX-2. RESULTS Inflammation was evident in all lobes of the prostate with the DLP most severely affected. Infection consistently led to a significant increase in neutrophils and macrophages in the early stages of prostate infection, followed by lymphocytic inflammation at the later time points. Inflammation was accompanied by induction of several inflammatory genes, including IL-1 family members, IL-6, and COX-2, and induced a significant increase in epithelial proliferation and reactive hyperplasia in all three prostate lobes. CONCLUSIONS Transurethral inoculation of uropathogenic E. coli 1677 reliably infects the mouse prostate, produces a significant inflammatory response, and induces quantifiable epithelial proliferation and reactive hyperplasia.

Prostatic inflammation enhances basal-to-luminal differentiation and accelerates initiation of prostate cancer with a basal cell origin

“…As described in detail in Materials and Methods, the CP9 E. coli and PBS control solutions were inoculated transurethrally into 9-wk-old wild-type C57BL/6 male mice. Consistent with previous reports, there were significantly variable degrees of inflammation among experimental mice and among different prostatic lobes (7,32). In addition, inflamed and noninflamed ducts often were observed concomitantly in all different lobes.…”

“…One reason for chronic inflammation in the prostate is bacterial colonization in the prostate via reflux of urine into the prostatic ducts of the peripheral zone (31). A reproducible mouse model of bacterial prostatitis has been established in which transurethral inoculation of uropathogenic strains of Escherichia coli into the prostate results in massive inflammation and reactive hyperplasia in the prostate (7,(32)(33)(34). As reported here, we established this mouse model for prostatitis using a uropathogenic E. coli strain CP9 that was isolated from the blood of a patient with pyelonephrititis (35).…”

AIM2, an IFN-Inducible Cytosolic DNA Sensor, in the Development of Benign Prostate Hyperplasia and Prostate Cancer

“…Accordingly, studies have found an increased relative risk of prostate cancer in men with a prior history of certain sexually transmitted infections or prostatitis, which are often associated with intraprostatic inflammation (6,7). Furthermore, studies have indicated possible links between certain prostatic infections and inflammation (6,7,11,12).…”

Pathogenetic Influences of Human Herpesvirus 8 (HHV-8) in Prostate Cancer Progression

“…Recently, inflammation has been proposed as a contributing factor to both prostate cancer initiation and progression (99,100), and it has been demonstrated that P. acnes and uropathogenic E. coli infections have been shown to strongly elicit inflammatory responses and enhance prostate cell proliferation (122)(123)(124) Together these results suggest that HHV-8 promotes an androgen-independent phenotype that does not require activation of and is potentially independent of the AR signaling pathway. Figure 6).…”

“…Propionibacterium acnes and Escherichia coli infections of benign prostate cells induce significant changes in cell proliferation rates (122)(123)(124). However, to our knowledge, no studies have assessed how a chronic infection of malignant but otherwise androgensensitive prostate cells would affect disease course.…”