Elsevier

Urology

Volume 75, Issue 4, April 2010, Pages 933-937
Urology

Interstitial Cystitis, Chronic Pelvic Pain, and Infection
Elevated Urinary Levels and Urothelial Expression of Hepatocarcinoma-intestine-pancreas/Pancreatitis-associated Protein in Patients With Interstitial Cystitis

https://doi.org/10.1016/j.urology.2009.05.044Get rights and content

Objectives

To investigate the pathophysiology of interstitial cystitis (IC), we examined urinary levels and urothelial expression of human orthologue of pancreatitis-associated protein (PAP) III, namely, hepatocarcinoma-intestine-pancreas (HIP)/PAP, in patients with IC. We have previously shown that PAP III is expressed with increased frequency in the bladder urothelium in a rat cystitis model (Takahara Y, et al. J Urol. 2008;179:1603-1609).

Methods

HIP/PAP levels in the urine from patients with IC were measured by enzyme-linked immunosorbent assay, and HIP/PAP expression in the bladder tissues was assessed by immunohistochemical study.

Results

The median concentration of urinary HIP/PAP was significantly higher in patients with IC than in controls (13.67 vs 1.86 pg/mL urine, respectively, P <.0001, with Mann–Whitney U test). HIP/PAP immunoreactivity was observed in the urothelium of 88.2% of patients with IC (15/17) and in 5.9% of bladder tissues of controls (1/17). Urinary HIP/PAP levels in patients with IC were positively correlated with urinary frequency and bladder pain (r = 0.429, 0.443) and inversely correlated with mean voided urine volume (r = −0.488).

Conclusions

Urinary HIP/PAP levels were significantly higher in IC patients and the apparent HIP/PAP expression in the bladder urothelium was more frequently observed among IC patients. The involvement of HIP/PAP in the pathophysiology of IC is suggested.

Section snippets

Patients

We followed our institution's ethics guidelines and the study was approved by the ethics committee of the Osaka City University Hospital. All patients provided informed consent. Patients with IC were diagnosed based on the National Institute of Diabetes and Digestive and Kidney Diseases clinical criteria. The 24-hour urinary frequency and mean voided urine volume were assessed by a voiding diary and bladder pain on a verbal 11-point rating scale (VRS). The VRS is a common pain scale for rating

HIP/PAP Levels in the Urine

Urinary specimens were collected from 27 female IC patients (median age: 58 years, range: 31-83 years) and from 27 female controls (median age: 58 years, range: 30-81 years). No samples had bacterial urinary tract infection. The median urinary HIP/PAP concentration was significantly higher in IC patients than in controls (Fig. 1).

Immunohistochemical Localization of HIP/PAP in the Bladder

Bladder tissues from 17 female IC patients (median age: 58 years, range: 30-82 years) were processed for immunohistochemistry, using an antibody specific to HIP/PAP.

Comment

In this study, we have demonstrated that the urinary HIP/PAP levels in IC patients were apparently higher than those in normal controls. Increased immunoreactivity for HIP/PAP was frequently observed in the umbrella cells of the urothelium in IC patients, suggesting that expression of HIP/PAP is induced in the urothelium and HIP/PAP is released into the urine in IC patients. Intriguingly, the urinary levels of HIP/PAP are correlated with the severity of urinary symptoms, implying that the level

Conclusions

We revealed that HIP/PAP levels in the urine were significantly higher in IC patients than in controls, and HIP/PAP expression in the urothelium was frequently observed in IC patients. Because we found a significant association between urinary HIP/PAP levels and urinary symptoms in IC patients, it is concluded that HIP/PAP may be involved in the pathogenesis of IC.

Acknowledgments

J.L. Iovanna, INSERM U.624, Marseille, France, provided information about PAP enzyme-linked immunosorbent assay system.

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This work was supported by grants from Ministry of Health, Labour and Welfare of Japan, MEXT Japan, and Osaka City University.

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