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. 2013 Jun;73(9):1007-15.
doi: 10.1002/pros.22648. Epub 2013 Feb 6.

A mouse model of chronic prostatic inflammation using a human prostate cancer-derived isolate of Propionibacterium acnes

Debika Biswal Shinohara  1 , Ajay M Vaghasia, Shu-Han Yu, Tim N Mak, Holger Brüggemann, William G Nelson, Angelo M De Marzo, Srinivasan Yegnasubramanian, Karen S Sfanos
Affiliations

A mouse model of chronic prostatic inflammation using a human prostate cancer-derived isolate of Propionibacterium acnes

Debika Biswal Shinohara et al. Prostate. 2013 Jun.

Abstract

Background: Prostatic inflammation has been linked to a number of prostatic diseases such as benign prostatic hyperplasia (BPH), prostatitis syndromes, and prostate cancer. Major unanswered questions include what pathogenic mechanisms, such as bacterial infections, may drive the accumulation of inflammatory infiltrates in the human prostate, and how inflammation might contribute to disease. To study this potential link in an in vivo system, we developed a mouse model of long-term bacteria-induced chronic inflammation of the prostate using a human prostatectomy-derived strain of Propionibacterium acnes.

Methods: C57BL/6J mice were inoculated, via urethral catheterization, with vehicle control or a prostatectomy-derived strain of P. acnes (PA2). Animals were assessed at 2 days, 1, 2, or 8 weeks post-inoculation via histology and immunohistochemistry (IHC).

Results: PA2 inoculation resulted in severe acute and chronic inflammation confined to the dorsal lobe of the prostate. Chronic inflammation persisted for at least 8 weeks post-inoculation. Inflammatory lesions were associated with an increase in the Ki-67 proliferative index, and diminished Nkx3.1 and androgen receptor (AR) production. Interestingly, the observed response required live bacteria and both IHC and in situ hybridization assays for P. acnes indicated a potential intracellular presence of P. acnes in prostate epithelial cells.

Conclusions: To our knowledge, this is the first mouse model of long-term prostatic inflammation induced by P. acnes, and more generally, any prostatectomy-derived bacterial isolate. This model may serve as a valuable preclinical model of chronic prostatic inflammation that can be used to mechanistically study the link between inflammation and prostatic disease.

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Figures

Fig. 1
Fig. 1
Dorsal prostate of C57BL/6J mice 1,2, or 8 weeks after inoculation of either PBS (control) or PA2 P. acnes via urethral catheterization. Accumulations of neutrophils were observed in the glandular lumens (arrows) at 1 and 2 weeks post-inoculation. Accumulations of chronic inflammatory cells in the stroma (arrowheads) were observed at all time points starting at 1 week post-inoculation. Bottom row is enlarged view of boxed area in panel above.
Fig. 2
Fig. 2
Prevalence (A) and extent (B) of inflammation in mouse dorsal prostate lobes after PA2 P. acnes infection.
Fig. 3
Fig. 3
Detection of P. acnes in mouse dorsal prostate. IHC (A,B) and 1SH (C) for P. acnes at I week post-inoculation. IHC for P. acnes 2 weeks post-inoculation (D,E) and 8 weeks post-inoculation (F). Note positive staining for P. acnes cells in prostate-infiltrating neutrophils (arrows pointing to representative examples) and prostate epithelium (arrowheads pointing to representative examples).
Fig. 4
Fig. 4
Increased proliferative index of inflamed dorsal prostate. IHC for Ki-67 1, 2, and 8 weeks post-inoculation with PA2 P. acnes. Note increased Ki-67 nuclear staining in epithelium of inflamed glands (arrowheads) versus non-inflamed glands (arrows).
Fig. 5
Fig. 5
IHC for Nkx3.1 and AR in P. acnes infected mouse dorsal prostate at I (top row) and 2 weeks (bottom row) post-inoculation. Note diminished Nkx3.1 and AR staining in epithelial cells of inflamed glands (arrowheads) versus non-inflamed glands (arrows).
See this image and copyright information in PMC

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