Abstract
ObjectiveThis study was designed to investigate whether increased urothelial cell apoptosis and chronic inflammation might contribute to recurrent urinary tract infection (UTI) in women.MethodsThe bladder biopsy specimens were collected from thirty women with recurrent UTI and ten controls. The bladder biopsies were performed at one to two months after UTI episode had been completely resolved and urine analysis and urine culture all showed negative. Immunofluorescence staining of the adhesive protein E-cadherin, mast cell and TUNEL were performed in all the bladder specimens. In addition, western blots were also performed to analyze the inflammatory proteins (phospho-p38, tryptase) and apoptotic protein (Bax) in the bladder mucosa specimens between patients with recurrent UTI and controls.ResultsImmunofluorescence staining showed significantly lower E-cadherin in the recurrent UTI bladder tissue compared with the controls (25.4±8.9 v 42.4±16.7, p<0.0001). The mast cell expression was significantly stronger in the recurrent UTI bladder tissue compared with the controls (2.5±1.8 v 1.3±1.2, p = 0.046). TUNEL staining revealed a significantly higher numbers of apoptotic cells in the recurrent UTI bladder tissue compared with the control bladder tissue (1.5±1.8 v 0.08±0.3, p<0.0001). Western blot analysis also showed that the expressions of tryptase and Bax increased in five recurrent UTI specimens compared with two normal control specimens.ConclusionChronic inflammation, urothelial cell apoptosis and impairment of barrier function of urothelial cells might contribute to recurrent UTI in women.
Highlights
Recurrent urinary tract infection (UTI) is a very bothersome and a popular problem in the urogynecology clinical practice
Ecadherin immunolabelling was widely distributed in the cell-cell junctions in the superficial layers of the urothelium of the normal control specimen, suburothelial layers showed no immunoreactivity for E-cadherin (Fig. 1)
TUNEL staining revealed a significantly higher numbers of apoptotic cells in the recurrent UTI bladder tissue compared with the control bladder tissue (1.561.8 v 0.0860.3, p,0.0001). (Table 1) There were almost no apoptotic cells (TUNEL staining positive) in the control tissue, some apoptotic cells were distributed in the urothelium as well as suburothelium of recurrent UTI bladder tissue (Fig. 1)
Summary
Recurrent urinary tract infection (UTI) is a very bothersome and a popular problem in the urogynecology clinical practice. According to the IUGA/ICS joint report on the terminology for female pelvic floor dysfunction, recurrent UTI is defined as at least three symptomatic and medically diagnosed UTI in the previous 12 months. Recurrent UTI is one of the most common diagnoses for female pelvic floor dysfunction [1]. Interstitial cystitis/bladder pain syndrome (IC/BPS) is a known chronic inflammatory disorder of the urinary bladder. Overactive bladder (OAB) is another subject to be linked to chronic bladder inflammation. Some inflammatory biomarkers such as nerve growth factor (NGF), cytokines and serum C-reactive protein are increased in patients with OAB and those with IC/BPS [6,7,8,9,10,11,12]
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