title: The NLRP3 Inflammasome Mediates Inflammation Produced by Bladder Outlet Obstruction.
abstract: OBJECTIVE
  While bladder outlet obstruction is well established to elicit an inflammatory reaction in the bladder that leads to overactive bladder and fibrosis, little is known about the mechanism by which this is initiated. NLRs (NOD-like receptors) and the structures that they form (inflammasomes) have been identified as sensors of cellular damage, including pressure induced damage, and triggers of inflammation. Recently we identified these structures in the urothelium. In this study we assessed the role of the NLRP3 (NACHT, LRR and PYD domains-containing protein 3) inflammasome in bladder dysfunction resulting from bladder outlet obstruction.
  
  
  METHODS
  Bladder outlet obstruction was created in female rats by inserting a 1 mm outer diameter transurethral catheter, tying a silk ligature around the urethra and removing the catheter. Untreated and sham operated rats served as controls. Rats with bladder outlet obstruction were given vehicle (10% ethanol) or 10 mg/kg glyburide (a NLRP3 inhibitor) orally daily for 12 days. Inflammasome activity, bladder hypertrophy, inflammation and bladder function (urodynamics) were assessed.
  
  
  RESULTS
  Bladder outlet obstruction increased urothelial inflammasome activity, bladder hypertrophy and inflammation, and decreased voided volume. Glyburide blocked inflammasome activation, reduced hypertrophy and prevented inflammation. The decrease in voided volume was also attenuated by glyburide mechanistically as an increase in detrusor contraction duration and voiding period.
  
  
  CONCLUSIONS
  Results suggest the importance of the NLRP3 inflammasome in the induction of inflammation and bladder dysfunction secondary to bladder outlet obstruction. Arresting these processes with NLRP3 inhibitors may prove useful to treat the symptoms that they produce.
authors.affiliation: Division of Urology, Department of Surgery, Duke University Medical Center, Durham, North Carolina; Department of Urology, Medical University of South Carolina, Charleston, South Carolina.
authors.forename: Francis M
authors.initials: FM
authors.lastname: Hughes
authors.affiliation: Department of Urology, Medical University of South Carolina, Charleston, South Carolina.
authors.forename: Hayden M
authors.initials: HM
authors.lastname: Hill
authors.affiliation: Department of Urology, Medical University of South Carolina, Charleston, South Carolina.
authors.forename: Case M
authors.initials: CM
authors.lastname: Wood
authors.affiliation: Department of Urology, Medical University of South Carolina, Charleston, South Carolina.
authors.forename: Andrew T
authors.initials: AT
authors.lastname: Edmondson
authors.affiliation: Department of Urology, Medical University of South Carolina, Charleston, South Carolina.
authors.forename: Aliya
authors.initials: A
authors.lastname: Dumas
authors.affiliation: Department of Pathology, Duke University Medical Center, Durham, North Carolina.
authors.forename: Wen-Chi
authors.initials: WC
authors.lastname: Foo
authors.affiliation: Department of Urology, Medical University of South Carolina, Charleston, South Carolina.
authors.forename: James M
authors.initials: JM
authors.lastname: Oelsen
authors.affiliation: Department of Urology, Medical University of South Carolina, Charleston, South Carolina.
authors.forename: Goran
authors.initials: G
authors.lastname: Rac
authors.affiliation: Division of Urology, Department of Surgery, Duke University Medical Center, Durham, North Carolina; Department of Urology, Medical University of South Carolina, Charleston, South Carolina. Electronic address: todd.purves@duke.edu.
authors.forename: J Todd
authors.initials: JT
authors.lastname: Purves
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D007113:Immunity, Innate; D007150:Immunohistochemistry; D058847:Inflammasomes / Q000276:immunology / Q000378:metabolism*; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D001748:Urinary Bladder Neck Obstruction / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D019459:Urothelium / Q000276:immunology / Q000378:metabolism / Q000473:pathology
chemical_list: D058847:Inflammasomes; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C573346:Nlrp3 protein, rat
keywords: cystitis; immunity; inflammasomes; inflammation; innate; urinary bladder neck obstruction