Exaggerated expression of inflammatory mediators in vasoactive intestinal polypeptide knockout (VIP-/-) mice with cyclophosphamide (CYP)-induced cystitis.
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-1beta and CXCL1. CYP treatment significantly (p < or = 0.001) increased expression of CXCL1 and IL-1beta in the urinary bladder of WT and VIP(-/-) mice, but expression in VIP(-/-) mice with CYP treatment was significantly (p < or = 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.
Girard
Beatrice M
BM
Department of Anatomy and Neurobiology, University of Vermont College of Medicine, Burlington, VT, USA.
Malley
Susan E
SE
Braas
Karen M
KM
Waschek
James A
JA
May
Victor
V
Vizzard
Margaret A
MA
D000818:Animals; D003520:Cyclophosphamide / Q000494:pharmacology*; D003556:Cystitis / Q000139:chemically induced* / Q000378:metabolism; D016207:Cytokines / Q000276:immunology*; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D001743:Urinary Bladder / Q000502:physiology / Q000503:physiopathology; D014554:Urination / Q000502:physiology; D014660:Vasoactive Intestinal Peptide / Q000235:genetics / Q000378:metabolism
D016207:Cytokines; D014660:Vasoactive Intestinal Peptide; D003520:Cyclophosphamide