Login to Access Video or Poster Abstract: MP17-01
Sources of Funding: NIDDK,U54 DK112079

Introduction

Large clinical studies have implicated prostatic inflammation as a major player in the progression of benign prostatic hyperplasia (BPH). However, the molecular mechanisms that contribute to the inflammation in BPH remain unexplored. Animal studies on prostatic inflammation demonstrated a role for inflammasome in interleukin-18 (IL-18) expression. The role of inflammasome in BPH is unclear, but the expression of IL-18 was reported in biopsy of BPH patients. Here, we investigated the expression of a major inflammasome component called nucleotide-binding oligomerization domain-like receptor with pyrin domain protein 1 (NLRP) 1 and its downstream cytokine IL-18 in prostate specimens of BPH patients._x000D_

Methods

Slides containing the cryosections of prostatectomy specimens of Caucasian BPH patients (40-79 years) negative for cancer (n=4) were acquired from the health sciences tissue bank at the University of Pittsburgh following the IRB# 0506140. Intra-prostatic inflammatory infiltration was assessed by H&E staining. Immunofluorscence of inflammasome and IL-18 was assessed using primary antibodies for NALP1 (1:200); and IL-18 (1:50) at 4°C for 12h followed by 2 h incubation at 25°C with secondary donkey antibody tagged to Alexa Fluor 488 or Alexa Flour 594 (1: 200). Banked urine specimens from controls and BPH patients were analyzed for IL-18 levels.

Results

BPH specimens remarkable for hyperplastic nodules of glands (Fig.1A) and absence of inflammation failed to show the co-localization of red and green immunoreactivity for IL-18 and NLRP1 inflammasome, respectively (Fig.1C).BPH specimens marked by stromal enlargement and infiltration of inflammatory cells (&[larr], Fig.1B) also showed the co-localization of red and green immunoreactivity for IL-18 and NLRP1 inflammasome against the blue DAPI background (red arrowhead in Fig.1D) IL-18 levels were elevated in banked urine specimens of BPH patients._x000D_

Conclusions

Co-localized immunoreactivity of NLRP1, and its downstream product IL-18 supports the assembly and activation of inflammasome in BPH specimens positive for infiltration of inflammatory cells. Recapitulation of findings from the animal model demonstrate that inflammasome plays a major role in the prostatic inflammation associated with BPH and therefore inflammasome targeted therapies can be an option for BPH management.

Funding

NIDDK,U54 DK112079