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Inflammasomes are important mediators of prostatic inflammation associated with BPH

Kashyap, M and Pore, S and Wang, Z and Gingrich, J and Yoshimura, N and Tyagi, P (2015) Inflammasomes are important mediators of prostatic inflammation associated with BPH. Journal of Inflammation (United Kingdom), 12 (1).

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Abstract

© 2015 Kashyap et al. 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.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Kashyap, Mmpk39@pitt.eduMPK39
Pore, Sskp31@pitt.eduSKP31
Wang, Zwangz2@pitt.eduWANGZ2
Gingrich, Jjrg26@pitt.eduJRG26
Yoshimura, Nnyos@pitt.eduNYOS
Tyagi, Pprt18@pitt.eduPRT18
Date: 17 May 2015
Date Type: Publication
Journal or Publication Title: Journal of Inflammation (United Kingdom)
Volume: 12
Number: 1
DOI or Unique Handle: 10.1186/s12950-015-0082-3
Schools and Programs: School of Medicine > Urology
Refereed: Yes
Date Deposited: 11 Aug 2016 18:15
Last Modified: 04 Feb 2019 15:56
URI: http://d-scholarship.pitt.edu/id/eprint/29273

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