Evidence for Urothelial Cell Activation in Interstitial Cystitis

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Abstract
Bladder biopsy samples from 17 interstitial cystitis patients and 20 controls were evaluated for urothelial cell activation using a panel of monoclonal antibodies to HLA-DR, intercellular adhesion molecule 1, interleukin 1 alpha and tumor necrosis factor alpha. Urothelial cells in the majority (13 of 16, 81%) of the biopsies from patients with interstitial cystitis showed increased expression of HLA-DR, while fewer samples were positive for intercellular adhesion molecule 1 (3 of 16, 19%), interleukin 1 alpha (2 of 17, 12%) or tumor necrosis factor alpha (1 of 15, 7%). No urothelial cell expression of intercellular adhesion molecule 1, interleukin 1 alpha or tumor necrosis factor alpha was detected in the controls, and only 1 of 20 control samples contained HLA-DR positive urothelial cells. These results suggest that an unusual type of cellular activation is present in interstitial cystitis. In vitro studies with cultured normal urothelial cells indicated that cells activated with gamma interferon and tumor necrosis factor alpha expressed intercellular adhesion molecule 1 and HLA-DR, although increases in intercellular adhesion molecule 1 expression occurred earlier. Urothelial cells in interstitial cystitis patients may be defective in ability to express intercellular adhesion molecule 1. Alternatively, the differential expression of HLA-DR and intercellular adhesion molecule 1 in interstitial cystitis specimens may represent a functional subset of interstitial cystitis or reflect different stages of the disease. Urothelial cell activation in interstitial cystitis may result in aberrant immune responses and immune activation within the bladder. Because HLA-DR can be detected in paraffin-embedded tissues, evaluation of urothelial cell HLA-DR expression, although not specific for interstitial cystitis, may become a useful tool in the pathological evaluation of biopsy tissues from patients with this disease.

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