title: A mouse model of chronic prostatic inflammation using a human prostate cancer-derived isolate of Propionibacterium acnes.
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.
authors: Department of Environmental Health Sciences, Bloomberg School of Public Health, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors: Debika Biswal
authors: DB
authors: Shinohara
authors: Ajay M
authors: AM
authors: Vaghasia
authors: Shu-Han
authors: SH
authors: Yu
authors: Tim N
authors: TN
authors: Mak
authors: Holger
authors: H
authors: Brüggemann
authors: William G
authors: WG
authors: Nelson
authors: Angelo M
authors: AM
authors: De Marzo
authors: Srinivasan
authors: S
authors: Yegnasubramanian
authors: Karen S
authors: KS
authors: Sfanos
mesh_terms: D000818:Animals; D002908:Chronic Disease; D004195:Disease Models, Animal; D016908:Gram-Positive Bacterial Infections / Q000382:microbiology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011425:Propionibacterium acnes / Q000254:growth & development* / Q000302:isolation & purification; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000382:microbiology* / Q000601:surgery; D011472:Prostatitis / Q000382:microbiology*
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