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

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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.

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Acknowledgements

This work was funded by NIH grants DK051369, DK060481, and DK065989. The authors gratefully acknowledge the technical expertise and support provided for the superarray by the Vermont Cancer Center DNA Analysis Facility. This project was also supported by NIH Grant Number P20 RR16435 from the COBRE Program of the National Center for Research Resources.

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  1. Department of Anatomy and Neurobiology, University of Vermont College of Medicine, Burlington, VT, USA

    Beatrice M. Girard, Karen M. Braas, Victor May & Margaret A. Vizzard

  2. Department of Neurology, University of Vermont College of Medicine, D415A Given Research Building, Burlington, VT, 05405, USA

    Susan E. Malley & Margaret A. Vizzard

  3. University of California, Los Angeles, CA, USA

    James A. Waschek

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  1. Beatrice M. Girard
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Correspondence to Margaret A. Vizzard.

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Girard, B.M., Malley, S.E., Braas, K.M. et al. Exaggerated Expression of Inflammatory Mediators in Vasoactive Intestinal Polypeptide Knockout (VIP−/−) Mice with Cyclophosphamide (CYP)-Induced Cystitis. J Mol Neurosci 36, 188–199 (2008). https://doi.org/10.1007/s12031-008-9084-4

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