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Updated: May 3, 2026
Author Spotlight: Developing Parmodulins to Target Protease-Activated Receptors for Inflammation Control
Published on: May 24, 2024
Proteinase-activated receptor-1 and immunomodulatory effects of a PAR1-activating peptide in a mouse model of
M Mark Stanton1, Lisa K Nelson1, Hallgrimur Benediktsson2
1Department of Biological Sciences, University of Calgary, 2500 University Drive NW, Calgary, AB, Canada T2N 1N4 ; Inflammation Research Network, University of Calgary, 2500 University Drive NW, Calgary, AB, Canada T2N 1N4 ; Biofilm Research Group, University of Calgary, 2500 University Drive NW, Calgary, AB, Canada T2N 1N4.
Background:
Nonbacterial prostatitis has no established etiology. We hypothesized that proteinase-activated receptor-1 (PAR1) can play a role in prostatitis. We therefore investigated the effects of PAR1 stimulation in the context of a new model of murine nonbacterial prostatitis.
Methods:
Using a hapten (ethanol-dinitrobenzene sulfonic acid- (DNBS-)) induced prostatitis model with both wild-type and PAR1-null mice, we examined (1) the location of PAR1 in the mouse prostate and (2) the impact of a PAR1-activating peptide (TFLLR-NH2: PAR1-TF) on ethanol-DNBS-induced inflammation.
Results:
Ethanol-DNBS-induced inflammation was maximal at 2 days. In the tissue, PAR1 was expressed predominantly along the apical acini of prostatic epithelium. Although PAR1-TF on its own did not cause inflammation, its coadministration with ethanol-DNBS reduced all indices of acute prostatitis. Further, PAR1-TF administration doubled the prostatic production of interleukin-10 (IL-10) compared with ethanol-DNBS treatment alone. This enhanced IL-10 was not observed in PAR1-null mice and was not caused by the reverse-sequence receptor-inactive peptide, RLLFT-NH2. Surprisingly, PAR1-TF, also diminished ethanol-DNBS-induced inflammation in PAR1-null mice.
Conclusions:
PAR1 is expressed in the mouse prostate and its activation by PAR1-TF elicits immunomodulatory effects during ethanol-DNBS-induced prostatitis. However, PAR1-TF also diminishes ethanol-DNBS-induced inflammation via a non-PAR1 mechanism by activating an as-yet unknown receptor.
Insights
Proteinase-activated receptor-1 (PAR1) activation modulates inflammation in a mouse model of nonbacterial prostatitis. PAR1-activating peptide (PAR1-TF) reduced prostatitis and increased IL-10, but also acted via a non-PAR1 pathway.
Area of Science:
- Urology
- Immunology
- Gastroenterology
Background:
- Nonbacterial prostatitis lacks a defined cause.
- Proteinase-activated receptor-1 (PAR1) is a potential factor in prostatitis.
- Investigated PAR1's role in a novel murine prostatitis model.
Purpose of the Study:
- To determine the role of PAR1 in nonbacterial prostatitis.
- To examine the effects of PAR1 stimulation on inflammation in a murine model.
Main Methods:
- Utilized a hapten (ethanol-dinitrobenzene sulfonic acid [DNBS]) induced prostatitis model.
- Examined wild-type and PAR1-null mice.
- Assessed PAR1 location and the impact of PAR1-activating peptide (PAR1-TF) on inflammation.
Main Results:
- PAR1 was found in prostatic epithelium.
- PAR1-TF reduced DNBS-induced prostatitis and increased interleukin-10 (IL-10) production.
- PAR1-TF also reduced inflammation in PAR1-null mice, suggesting a non-PAR1 mechanism.
Conclusions:
- PAR1 is present in the prostate and influences inflammation.
- PAR1 activation by PAR1-TF has immunomodulatory effects.
- PAR1-TF exhibits a dual mechanism, involving both PAR1 and an unknown receptor.
