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

Authors

  • Debika Biswal Shinohara,

    1. Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University School of Medicine, Baltimore, Maryland
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  • Ajay M. Vaghasia,

    1. Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland
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  • Shu-Han Yu,

    1. Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland
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  • Tim N. Mak,

    1. Department of Biomedicine, Aarhus University, Aarhus, Denmark
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  • Holger Brüggemann,

    1. Department of Biomedicine, Aarhus University, Aarhus, Denmark
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  • William G. Nelson,

    1. Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University School of Medicine, Baltimore, Maryland
    2. Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland
    3. Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland
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  • Angelo M. De Marzo,

    1. Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland
    2. Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland
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  • Srinivasan Yegnasubramanian,

    1. Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University School of Medicine, Baltimore, Maryland
    2. Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland
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  • Karen S. Sfanos

    Corresponding author
    1. Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland
    2. Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, Maryland
    • Johns Hopkins University School of Medicine, 1550 Orleans Street, CRBII 1M43, Baltimore, MD 21287.
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  • Disclosure Statement: A.M.D. is currently an employee of Predictive Biosciences, Inc. who also holds a part-time adjunct appointment at the Johns Hopkins University School of Medicine. However, no funding or other support was provided by the company for any of the work in this manuscript. The terms of the relationship between A.M.D. and Predictive Biosciences are managed by the Johns Hopkins University in accordance with its conflict-of-interest policies.

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. Prostate 73: 1007–1015, 2013. © 2013 Wiley Periodicals, Inc.

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