Proteinase-Activated Receptor-1 and Immunomodulatory Effects of a PAR1-Activating Peptide in a Mouse Model of Prostatitis

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dc.contributor.authorStanton, M. Mark
dc.contributor.authorNelson, Lisa K.
dc.contributor.authorBenediktsson, Hallgrimur
dc.contributor.authorHollenberg, Morley D.
dc.contributor.authorBuret, Andre G.
dc.contributor.authorCeri, Howard
dc.date.accessioned2018-09-27T11:40:52Z
dc.date.available2018-09-27T11:40:52Z
dc.date.issued2013-12-29
dc.date.updated2018-09-27T11:40:52Z
dc.description.abstractBackground. 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.
dc.description.versionPeer Reviewed
dc.identifier.citationM. Mark Stanton, Lisa K. Nelson, Hallgrimur Benediktsson, Morley D. Hollenberg, Andre G. Buret, and Howard Ceri, “Proteinase-Activated Receptor-1 and Immunomodulatory Effects of a PAR1-Activating Peptide in a Mouse Model of Prostatitis,” Mediators of Inflammation, vol. 2013, Article ID 748395, 12 pages, 2013. doi:10.1155/2013/748395
dc.identifier.doihttps://doi.org/10.1155/2013/748395
dc.identifier.urihttp://hdl.handle.net/1880/108261
dc.identifier.urihttps://doi.org/10.11575/PRISM/44929
dc.language.rfc3066en
dc.rights.holderCopyright © 2013 M. Mark Stanton et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
dc.titleProteinase-Activated Receptor-1 and Immunomodulatory Effects of a PAR1-Activating Peptide in a Mouse Model of Prostatitis
dc.typeJournal Article
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