Browsing by Author "Stanton, M. Mark"

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    Proteinase-activated receptor 1 (par1) elicits immunomodulatory effects in a mouse model of nonbacterial prostatitis
    (2012) Stanton, M. Mark; Buret, Andre G.; Ceri, Howard
    The prostate is an accessory reproductive gland that is found in all male mammals. This gland is prone to infection, inflammation, and cancer, making it one of the most disease-prone tissues in the body. Specifically, the role of Proteinase-Activated Receptor 1 (PARl) has not been addressed in the context of nonbacterial prostatitis. In this study, P ARl and P AR2 were localized primarily to the apical prostatic epithelium in C57BL/6 mice. Instillation of the PARl agonist TFLLR-NH2 into the mouse prostate significantly diminished dinitrobenzene sulfonic acid (DNBS)-induced prostatitis. Furthermore, TFLLR-NH2 also elicited non-PARl-rnediated imrnunornodulatory effects that were protective against DNBS-induced prostatitis. TFLLR-NH2 directly up-regulated anti­inflammatory IL-10 production and the source of this IL-10 elevation was not macrophage-driven. Overall, these findings support an immunomodulatory role for P ARI in the mouse prostate and may present a pharmacological therapy for nonbacterial prostatitis.
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    Proteinase-Activated Receptor-1 and Immunomodulatory Effects of a PAR1-Activating Peptide in a Mouse Model of Prostatitis
    (2013-12-29) Stanton, M. Mark; Nelson, Lisa K.; Benediktsson, Hallgrimur; Hollenberg, Morley D.; Buret, Andre G.; Ceri, Howard
    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.