Exaggerated Expression of Inflammatory Mediators in Vasoactive Intestinal Polypeptide Knockout (VIP−/−) Mice with Cyclophosphamide (CYP)-Induced Cystitis

  • Beatrice M. Girard
  • Susan E. Malley
  • Karen M. Braas
  • James A. Waschek
  • Victor May
  • Margaret A. Vizzard
Article

Abstract

Vasoactive intestinal polypeptide (VIP) is an immunomodulatory neuropeptide distributed in micturition pathways. VIP−/− mice exhibit altered bladder function and neurochemical properties in micturition pathways after cyclophosphamide (CYP)-induced cystitis. Given VIP’s role as an anti-inflammatory mediator, we hypothesized that VIP−/− mice would exhibit enhanced inflammatory mediator expression after cystitis. A mouse inflammatory cytokine and receptor RT2 profiler array was used to determine regulated transcripts in the urinary bladder of wild type (WT) and VIP−/− mice with or without CYP-induced cystitis (150 mg/kg; i.p.; 48 h). Four binary comparisons were made: WT control versus CYP treatment (48 h), VIP−/− control versus CYP treatment (48 h), WT control versus VIP−/− control, and WT with CYP treatment (48 h) versus VIP−/− with CYP treatment (48 h). The genes presented represent (1) greater than 1.5-fold change in either direction and (2) the p value is less than 0.05 for the comparison being made. Several regulated genes were validated using enzyme-linked immunoassays including IL-1β and CXCL1. CYP treatment significantly (p ≤ 0.001) increased expression of CXCL1 and IL-1β in the urinary bladder of WT and VIP−/− mice, but expression in VIP−/− mice with CYP treatment was significantly (p ≤ 0.001) greater (4.2- to 13-fold increase) than that observed in WT urinary bladder (3.6- to 5-fold increase). The data suggest that in VIP−/− mice with bladder inflammation, inflammatory mediators are increased above that observed in WT with CYP. This shift in balance may contribute to increased bladder dysfunction in VIP−/− mice with bladder inflammation and altered neurochemical expression in micturition pathways.

Keywords

Micturition Cytokines Chemokines Inflammation 

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Copyright information

© Humana Press 2008

Authors and Affiliations

  • Beatrice M. Girard
    • 1
  • Susan E. Malley
    • 2
  • Karen M. Braas
    • 1
  • James A. Waschek
    • 3
  • Victor May
    • 1
  • Margaret A. Vizzard
    • 1
    • 2
  1. 1.Department of Anatomy and NeurobiologyUniversity of Vermont College of MedicineBurlingtonUSA
  2. 2.Department of NeurologyUniversity of Vermont College of MedicineBurlingtonUSA
  3. 3.University of CaliforniaLos AngelesUSA

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