Higher levels of cell apoptosis and abnormal E-cadherin expression in the urothelium are associated with inflammation in patients with interstitial cystitis/painful bladder syndrome

OBJECTIVE To investigate the relationships between suburothelial inflammation and urothelial dysfunction in interstitial cystitis/painful bladder syndrome (IC/PBlS). MATERIALS AND METHODS Immunofluorescence staining of ki-67 (to assess cell proliferation), junction protein E-cadherin, tryptase (to assess mast cell activation) and TUNEL (to assess urothelial apoptosis) were performed in bladder tissues from 20 patients with IC/PBlS and from 6 control patients. The fluorescence intensity of E-cadherin was measured using the ImageJ method. The percentage of apoptotic cells, proliferated cells and activated mast cells were measured and quantified as positive cells (+/-SD) per area unit (4 mu m(2)). RESULTS The ratio of ki-67-positive cells in the bladder tissue of the patients with IC/PBlS was significantly down-regulated compared with that of the control patients (0.559 +/- 0.658 vs. 1.23 +/- 1.28, P = 0.001). TUNEL staining revealed a significantly higher number of apoptotic cells in the IC/PBlS bladder tissue compared with control bladder tissue (2.26 +/- 2.04 v 0.051 +/- 0.124, P = 0.000). The tryptase signal was significantly stronger in the IC/PBlS bladder tissue compared with that of control patients (6.16 +/- 4.35 v 1.15 +/- 0.436, P = 0.000). The apoptotic cell number in IC/PBlS bladder tissue correlated significantly with mast cell activation (P = 0.021). Immunofluorescence also showed a significantly lower distribution of E-cadherin in IC/PBlS bladder tissue compared with that of control patients (8.50 +/- 6.83 v 17.2 +/- 11.9, P = 0.000). Lower expression of E-cadherin in IC/PBlS bladder tissue was significantly correlated with higher visual analogue pain scores in patients with IC/PBlS (P = 0.008). CONCLUSIONS The results of the present study suggest that urothelial homeostasis in IC/PBlS bladders was impaired, and abnormal urothelial function was significantly associated with chronic inflammation. The junctions between urothelial cells in IC/PBlS bladders were abnormal, which was associated with the patient's self-report pain scales.