Potential role of reluclear factor-kappaB in the pathogenesis of interstitial cystitis.

摘要

PURPOSE: Despite assertive investigation in the last 2 decades, interstitial cystitis remains an unresolved problem in clinical urology, and its etiology and the mechanisms involved in its pathogenesis are still a matter of conjecture. Recently nuclear factor (NF)-KB has been implicated in chronic inflammatory diseases, and is thought to be a key regulator of genes involved in response to infection, inflammation and stress. We document the presence, pattern and distribution of NF-kappaB in bladder biopsies from patients with interstitial cystitis. MATERIALS AND METHODS: Bladder biopsies from 7 women clinically diagnosed with interstitial cystitis according to National Institute for Diabetes and Digestive and Kidney Diseases criteria and 5 women diagnosed with urinary incontinence were used for immunohistochemical localization of p65, an NF-kappaB subunit. RESULTS: Our immunohistochemical localization experiments indicate that NF-kappaB was predominantly activated in bladder urothelial cells and cells of the submucosal layer in biopsies from patients with interstitial cystitis compared to controls. While activation was evident by intense nuclear localization of NF-kappaB in all interstitial cystitis specimens, diffuse and faint immunostaining was observed in control samples. The results also indicate that activation of NF-kappaB correlated with disease occurrence. CONCLUSIONS: The fact that NF-kappaB is capable of transactivating pro-inflammatory mediators, which in turn can amplify NF-kappaB activation by a positive regulatory loop, suggests that inflammatory and/or immune responses in interstitial cystitis can be exacerbated possibly by persistent activation of this nuclear factor. We believe that our study provides a novel basis for investigating the role of NF-kappaB activation in the pathophysiology of interstitial cystitis and further opens a frontier for the development of an innovative therapeutic approach to interstitial cystitis.