Physiol. Genomics Journal of Neurophysiology
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Physiol. Genomics 9: 5-13, 2002. First published February 12, 2002; doi:10.1152/physiolgenomics.00117.2001
1094-8341/02 $5.00
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Received 17 December 2001; accepted in final form 11 February 2002.
Physiological Genomics 9:5-13 (2002)
1094-8341/02 $5.00 © 2002 American Physiological Society

Changes in urinary bladder cytokine mRNA and protein after cyclophosphamide-induced cystitis

Susan E. Malley1 and Margaret A. Vizzard1,2

1 University of Vermont, College of Medicine, Departments of Neurology and Anatomy
2 Neurobiology, Burlington, Vermont 05405

Cyclophosphamide (CYP)-induced cystitis alters micturition function and produces reorganization of the micturition reflex. This reorganization may involve cytokine expression in the urinary bladder. These studies have determined candidate cytokines in the bladder that may contribute to the reorganization process. An RNase protection assay was used to measure changes in rat bladder cytokine mRNA [interferon-{gamma} (IFN)-{gamma}, interleukin-1{alpha}/ß (IL-1{alpha}/ß), IL-2, IL-3, IL-4, IL-5, IL-6, IL-10, and tumor necrosis factor-{alpha}/ß (TNF-{alpha}/ß)] after acute (4 h), intermediate (48 h), or chronic (10 day) cystitis. The correlation between bladder cytokine mRNA and protein expression was also determined by immunoassay. Although at each time point after cystitis significant changes in bladder cytokine mRNA were observed, the magnitude differed (acute > intermediate > chronic). Acute cystitis demonstrated the most robust changes (P <= 0.005; IL-1ß, 330-fold increase; IL-2, 20-fold increase; IL-4, 8-fold increase; IL-6, 80-fold increase) in cytokine mRNA expression and TNF-{alpha} or TNF-ß mRNA were only increased (2–10-fold) after acute cystitis. More modest increases in cytokine mRNA expression were observed after 48-h or 10-day cystitis. Cytokine protein expression generally paralleled that of mRNA. Increased cytokine expression after CYP-induced cystitis, alone or in combination with other inflammatory mediators or growth factors, may contribute to altered lower urinary tract function after cystitis.

inflammation; interleukins; tumor necrosis factor; neuroimmune interactions




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