title: Inflammasomes are important mediators of prostatic inflammation associated with BPH.
abstract: BACKGROUND
  There is mounting evidence to support the role of inflammation in benign prostate hyperplasia (BPH), and a recent study reported expression of inflammasome derived cytokine IL-18 in prostate biopsy of BPH patients. Here we examined the expression of inflammasome-derived cytokines and activation of nucleotide-binding oligomerization domain-like receptor with pyrin domain protein 1 (NLRP) 1 inflammasome in a rat model of prostatic inflammation relevant to BPH.
  
  
  METHODS
  Prostatic inflammation was experimentally induced in three-month-old male Sprague-Dawley rats by intraprostatic injection (50 μL) of either 5 % formalin or saline (sham) into the ventral lobes of prostate. 7 days later, prostate and bladder tissue was harvested for analysis of inflammasome by Western blot, immunohistochemistry and downstream cytokine production by Milliplex.
  
  
  RESULTS
  Expression of interleukins, CXC and CC chemokines were elevated 2-15 fold in formalin injected prostate relative to sham. Significant expression of NLRP1 inflammasome components and caspase-1 in prostate were associated with significant elevation of pro and cleaved forms of IL-1β (25.50 ± 1.16 vs 3.05 ± 0.65 pg/mg of protein) and IL-18 (1646.15 ± 182.61 vs 304.67 ± 103.95 pg/mg of protein). Relative to prostate tissue, the cytokine expression in bladder tissue was much lower and did not involve inflammasome activation.
  
  
  CONCLUSIONS
  Significant upregulation of NLRP1, caspase-1 and downstream cytokines (IL-18 and IL-1β) suggests that a NLRP1 inflammasome is assembled and activated in prostate tissue of this rat model . Recapitulation of findings from human BPH specimens suggests that the inflammasome may perpetuate the inflammatory state associated with BPH. Further clarification of these pathways may offer innovative therapeutic targets for BPH-related inflammation.
authors.affiliation: Department of Urology, University of Pittsburgh, Pittsburgh, USA.
authors.forename: Mahendra
authors.initials: M
authors.lastname: Kashyap
authors.affiliation: Department of Urology, University of Pittsburgh, Pittsburgh, USA.
authors.forename: Subrata
authors.initials: S
authors.lastname: Pore
authors.affiliation: Department of Urology, University of Pittsburgh, Pittsburgh, USA.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Urology, University of Pittsburgh, Pittsburgh, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Gingrich
authors.affiliation: Department of Urology, University of Pittsburgh, Pittsburgh, USA.
authors.forename: Naoki
authors.initials: N
authors.lastname: Yoshimura
authors.affiliation: Department of Urology, University of Pittsburgh, Pittsburgh, USA.
authors.forename: Pradeep
authors.initials: P
authors.lastname: Tyagi
keywords: BPH; Chemokines; IL-18; Inflammasome; NLRP1