MP08-05 BLADDER MACROPHAGE MIGRATION INHIBITORY FACTOR (MIF) RECEPTORS MEDIATE PAIN

You have accessJournal of UrologyBladder & Urethra: Anatomy, Physiology Pharmacology (MP08)1 Sep 2021MP08-05 BLADDER MACROPHAGE MIGRATION INHIBITORY FACTOR (MIF) RECEPTORS MEDIATE PAIN Shaojing Ye, Fei Ma, Dlovan Mahmood, Katherine Meyer-Siegler, Raymond Menard, David Hunt, Lin Leng, Richard Bucala, and Pedro Vera YeShaojing Ye More articles by this author , MaFei Ma MahmoodDlovan Mahmood Meyer-SieglerKatherine Meyer-Siegler MenardRaymond Menard HuntDavid Hunt LengLin Leng BucalaRichard Bucala VeraPedro View All Author Informationhttps://doi.org/10.1097/JU.0000000000001981.05AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: MIF, MIF receptors (CD74,CXCR4 OR CXCR2), high mobility group box1 (HMGB1) constitutively express inurothelium. Activation urothelialprotease activated receptor-4 (PAR4) induces bladder hyperalgesia (BHA). Wehypothesized that PAR4 elicits release urothelial binds tourothelial trigger the HMGB1 bladderpain through TLR4 receptors. The contribution specific intravesical MIFreceptors pathway is not clear. METHODS: Lower abdominal 50% mechanical threshold von Frey stimulation,measured before 24 hr after treatment, was used as an index BHA.Intravesical infusion (100 µM; 1 hr) under isoflurane induced acute BHA in C57BL/6J females (fig. 1A). Intravesical pre-treatment (10 min prior PAR4) with vehicles,isotype controls, neutralizing antibodies or CD74, antagonists toCD74 (MIF098, 200 μg), CXCR4 (AMD-3100, 50 μM), CXCR2 (SB225002, 6 μg),was applied study effect blocking on PAR4-induced BHA.Primary human normal cells (LifeLine Cell) were treated withvehicle, a antagonist (ISO-1, 100 µM), MIF-receptor (MIF098,10 μM AMD-3100, 5 μM) for 15 treatment (1 theculture medium collected. Released measured ELISA.Data analyzed ANOVA post-hoc tests. RESULTS: Pre-treatment neutralizingantibodies CD74 1B;C), (fig.1D;E), prevented significantly reduced pain andPAR4-induced intraluminal release. Pretreatment wasnot effective 1F). Similarly, antagonist, CD74or also fromhuman primary cells. CONCLUSIONS: Urothelial receptors, CXCR4mediate contribute pain. Blocking orMIF represent novel potential therapeutic targets Source Funding: DK121695(PLV); AR049610 (RB) © 2021 American Urological Association Education Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e151-e151 Advertisement Copyright Permissions© Inc.MetricsAuthor Information Expand Loading ...