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

Debika Biswal Shinohara, Ajay M. Vaghasia, Shu Han Yu, Tim N. Mak, Holger Brüggemann, William G Nelson, Angelo Michael Demarzo, S Yegnasubramanian, Karen Sfanos

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)1007-1015
Number of pages9
JournalProstate
Volume73
Issue number9
DOIs
StatePublished - Jun 2013

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Propionibacterium acnes
Prostatic Neoplasms
Inflammation
Prostate
Prostatectomy
Prostatic Diseases
Immunohistochemistry
Urinary Catheterization
Bacteria
Prostatitis
Androgen Receptors
Prostatic Hyperplasia
Inbred C57BL Mouse
Bacterial Infections
In Situ Hybridization
Histology
Epithelial Cells

Keywords

  • inflammation
  • mouse model
  • Propionibacterium acnes
  • prostate

ASJC Scopus subject areas

  • Urology
  • Oncology

Cite this

A mouse model of chronic prostatic inflammation using a human prostate cancer-derived isolate of Propionibacterium acnes. / Shinohara, Debika Biswal; Vaghasia, Ajay M.; Yu, Shu Han; Mak, Tim N.; Brüggemann, Holger; Nelson, William G; Demarzo, Angelo Michael; Yegnasubramanian, S; Sfanos, Karen.

In: Prostate, Vol. 73, No. 9, 06.2013, p. 1007-1015.

Research output: Contribution to journalArticle

Shinohara, Debika Biswal ; Vaghasia, Ajay M. ; Yu, Shu Han ; Mak, Tim N. ; Brüggemann, Holger ; Nelson, William G ; Demarzo, Angelo Michael ; Yegnasubramanian, S ; Sfanos, Karen. / A mouse model of chronic prostatic inflammation using a human prostate cancer-derived isolate of Propionibacterium acnes. In: Prostate. 2013 ; Vol. 73, No. 9. pp. 1007-1015.
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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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AU - Shinohara, Debika Biswal

AU - Vaghasia, Ajay M.

AU - Yu, Shu Han

AU - Mak, Tim N.

AU - Brüggemann, Holger

AU - Nelson, William G

AU - Demarzo, Angelo Michael

AU - Yegnasubramanian, S

AU - Sfanos, Karen

PY - 2013/6

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N2 - 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.

AB - 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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