Proteinase-activated receptor-1 and immunomodulatory effects of a PAR1-activating peptide in a mouse model of prostatitis.
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.
Department 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.
M Mark
MM
Stanton
Department 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.
Lisa K
LK
Nelson
Department of Pathology and Laboratory Medicine, Calgary Laboratory Services, Foothills Medical Centre, 1403 29 Street NW, Calgary, AB, Canada T2N 2T9.
Hallgrimur
H
Benediktsson
Inflammation Research Network, University of Calgary, 2500 University Drive NW, Calgary, AB, Canada T2N 1N4 ; Department of Physiology and Pharmacology, University of Calgary Health Sciences Center, 3330 Hospital Drive NW, Calgary, AB, Canada T2N 4N1.
Morley D
MD
Hollenberg
Department 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.
Andre G
AG
Buret
Department 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.
Howard
H
Ceri
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D004139:Dinitrofluorobenzene / Q000031:analogs & derivatives / Q000633:toxicity; D004195:Disease Models, Animal; D000431:Ethanol / Q000633:toxicity; D007155:Immunologic Factors / Q000494:pharmacology*; D016753:Interleukin-10 / Q000096:biosynthesis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009842:Oligopeptides / Q000494:pharmacology*; D011472:Prostatitis / Q000209:etiology / Q000276:immunology / Q000517:prevention & control*; D044463:Receptor, PAR-1 / Q000502:physiology*
D000893:Anti-Inflammatory Agents; D007155:Immunologic Factors; D009842:Oligopeptides; C462999:PAR-1-activating peptide; D044463:Receptor, PAR-1; D016753:Interleukin-10; C045305:2,4-dinitrofluorobenzene sulfonic acid; D000431:Ethanol; D004139:Dinitrofluorobenzene