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Prostate. 2015 Jan;75(1):23-32. doi: 10.1002/pros.22886. Epub 2014 Oct 4.

Resolution of chronic bacterial-induced prostatic inflammation reverses established fibrosis.

Author information

1
Department of Urology, University of Wisconsin-Madison, Madison, Wisconsin; Molecular and Environmental Toxicology Center, University of Wisconsin-Madison, Madison, Wisconsin.

Abstract

BACKGROUND:

Prostatic inflammation has been suggested to contribute to the etiology of lower urinary tract symptoms by inducing fibrosis. We previously used a well-characterized mouse model of bacterial-induced prostate inflammation to demonstrate that chronic prostatic inflammation induces collagen deposition. Here, we examined stability of the newly synthesized collagen in bacterial-induced prostatic inflammation and the reversibility of fibrosis after resolution of infection and inflammation.

METHODS:

Uropathogenic Escherichia coli 1677 was instilled transurethrally into adult C3H/HeOuJ male mice to induce chronic prostatic inflammation. Collagen was labeled by (3) H-proline administration for 28 days post-inoculation and (3) H-hydroxyproline incorporation measured to determine stability of the newly synthesized collagen. Inflammation score was graded using a previously established system and total collagen content was measured by picrosirius red staining quantitation and hydroxyproline content. Resolution of inflammation and reversal of collagen deposition was assessed after treatment with antibiotic enrofloxacin for 2 weeks on day 28 post-inoculation followed by an 8-week recovery period.

RESULTS:

Decay analysis of incorporated (3) H-hydroxyproline revealed the half-life of newly synthesized collagen to be significantly shorter in infected/inflamed prostates than in controls. Treatment with antibiotic enrofloxacin completely eradicated bacterial infection and allowed resolution of inflammation. This was followed by marked attenuation of collagen content and correlation analysis verified a positive association between the resolution of inflammation and the reversal of collagen deposition.

CONCLUSIONS:

These data demonstrate, for the first time, that inflammation-induced prostatic fibrosis is a reversible process.

KEYWORDS:

prostate; resolution of inflammation; reversibility of fibrosis

PMID:
25284058
PMCID:
PMC4257860
DOI:
10.1002/pros.22886
[Indexed for MEDLINE]
Free PMC Article

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