MP28-13 ACTIVATION OF INTRAVESICAL MACROPHAGE MIGRATION INHIBITORY FACTOR (MIF) RECEPTORS MEDIATES BLADDER PAIN

Abstract

You have accessJournal of UrologyBladder & Urethra: Anatomy, Physiology & Pharmacology I (MP28)1 Apr 2020MP28-13 ACTIVATION OF INTRAVESICAL MACROPHAGE MIGRATION INHIBITORY FACTOR (MIF) RECEPTORS MEDIATES BLADDER PAIN Shaojing Ye, Fei Ma, Katherine Meyer-Siegler, Lin Leng, Richard Bucala, and Pedro Vera* Shaojing YeShaojing Ye More articles by this author , Fei MaFei Ma More articles by this author , Katherine Meyer-SieglerKatherine Meyer-Siegler More articles by this author , Lin LengLin Leng More articles by this author , Richard BucalaRichard Bucala More articles by this author , and Pedro Vera*Pedro Vera* More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000867.013AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Activation of intravesical protease activated receptor-4 (PAR4) releases urothelial MIF to mediate release of urothelial high mobility group box1 (HMGB1) and mediate bladder pain. MIF receptors (CD74, CXCR2 OR CXCR4) are all localized within the urothelium and their role in bladder pain remains to be determined. We hypothesized that MIF mediates bladder pain by interacting with urothelial MIF receptors. Therefore, we tested whether intravesical antagonism of MIF reduces or prevents bladder pain. METHODS: PAR4 (100 µM; 1hr) was intravesically infused in female C57BL/6 mice under isoflurane anesthesia. Bladder pain (50% mechanical threshold on lower abdomen by von Frey (VF) stimulation) was measured before (baseline) and 24 hr post-PAR4 infusion. Scrambled PAR4 peptide (Scramb) was used as control. Intravesical pre-treatment (10 min prior to PAR4) with PBS, isotype control antibodies, neutralizing anti-MIF or anti-CD74 monoclonal antibodies, AMD-3100 (CXCR4 antagonist) and SB225002 (CXCR2 antagonist) tested the effect of specific MIF receptor antagonism on PAR4-induced bladder pain. Voided volume and frequency were also measured at 24 hr. At the end of experiments, bladders were collected for histology. ANOVA with Tukey post-hoc tests was used. RESULTS: Intravesical scrambled peptide did not produce bladder pain while intravesical PAR4 induced bladder pain. Pre-treatment with neutralizing anti-MIF or anti-CD74 antibodies, or CXCR4 antagonist prevented PAR4-induced bladder pain (Figure 1). Pretreatment with CXCR2 antagonist was not effective. No significant effects were noted on micturition volume while anti-CD74 pretreatment increased frequency slightly (Table 1). CONCLUSIONS: Intravesical MIF receptors (CD74 and CXCR4, but not CXCR2) mediate bladder pain. Future experiments will examine how intravesical antagonism of MIF or its receptors contributes to downstream mechanisms (e.g. release of urothelial HMGB1) that mediate bladder pain. Source of Funding: DK121695 (PLV); AR049610 (RB) © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e425-e425 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Shaojing Ye More articles by this author Fei Ma More articles by this author Katherine Meyer-Siegler More articles by this author Lin Leng More articles by this author Richard Bucala More articles by this author Pedro Vera* More articles by this author Expand All Advertisement PDF downloadLoading ...