MP28-11 ANNEXIN A1 INHIBITS NLRP3 AND PREVENTS INFLAMMATION DURING BLADDER OUTLET OBSTRUCTION

Abstract

You have accessJournal of UrologyBladder & Urethra: Anatomy, Physiology & Pharmacology I (MP28)1 Apr 2020MP28-11 ANNEXIN A1 INHIBITS NLRP3 AND PREVENTS INFLAMMATION DURING BLADDER OUTLET OBSTRUCTION Shelby N. Harper*, Francis M. Hughes, Brent D. Nose, Michael Zheng, Huixia Jin, and J. Todd Purves Shelby N. Harper*Shelby N. Harper* More articles by this author , Francis M. HughesFrancis M. Hughes More articles by this author , Brent D. NoseBrent D. Nose More articles by this author , Michael ZhengMichael Zheng More articles by this author , Huixia JinHuixia Jin More articles by this author , and J. Todd PurvesJ. Todd Purves More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000867.011AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Inflammation is a delicate balance between activators and inhibitors. A pivotal activator of inflammation is the NLRP3 inflammasome, which our lab has shown to be a central mediator of bladder inflammation in response to bladder outlet obstruction (BOO). However, little is known about endogenous inhibitors of inflammation within the bladder. Studies in other tissues have found Annexin A1 (ANXA1) has profound anti-inflammatory properties mediated through its interaction with the formyl peptide receptors (FPRs). One study has noted the presence of ANXA1 within bladder urothelia, but it is currently unknown if ANXA1 may interact with NLRP3 and/or inhibit inflammation in this tissue. In this study, we explore ANXA1’s relationship with NLRP3 in bladder urothelia in vitro and its ability to attenuate inflammation during BOO in vivo. METHODS: Female rats (∼200 g) were used. In vitro, primary urothelium were plated (o/n, 96-well plate), then treated with Ac2-26 for 1 hour followed by 0.625 mM ATP for an additional hour before being assayed for caspase-1 activity. Controls were treated with 1.25 mM ATP for maximal caspase activation. In vivo, rats underwent BOO surgery via insertion of a transurethral catheter (1 mm o.d.), tying of silk suture around the urethra, and removing the catheter. Ac2-26 (an ANXA1 mimetic; 1 mg/kg/day, i.p.) or PBS was administered for 12 days. Immunohistochemistry, Evans blue (inflammation), and caspase-1 (inflammasome activity) assays were then performed. RESULTS: In vitro, Ac2-26 decreased ATP-stimulated caspase-1 activity in a dose dependent fashion (figure 1). In vivo, immunocytochemistry showed ANXA1, FPR1 and FPR2 were present in bladder urothelium, while Ac2-26 decreased BOO-induced inflammasome activation and inflammation (figure 2). CONCLUSIONS: ANXA1 is a functional antagonist of NLRP3 and can suppress inflammation during BOO suggesting it may be a useful pharmacologic target for inflammatory conditions in the bladder. Source of Funding: NIDDK: R01DK103534 (PI- Purves) © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e424-e424 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Shelby N. Harper* More articles by this author Francis M. Hughes More articles by this author Brent D. Nose More articles by this author Michael Zheng More articles by this author Huixia Jin More articles by this author J. Todd Purves More articles by this author Expand All Advertisement PDF downloadLoading ...