POTENTIAL ROLE OF REL NUCLEAR FACTOR-KAPPA-B IN THE PATHOGENESIS OF INTERSTITIAL CYSTITIS/

Purpose: Despite assertive investigation in the last 2 decades, inters titial cystitis remains an unresolved problem in clinical urology, and its etiology and the mechanisms involved in its pathogenesis are stil l a matter of conjecture. Recently nuclear factor (NF)-kappa B has bee n 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- kappa B in bladder biopsies from patients with interstitial cystitis. Materials and Methods: Bladder biopsies from 7 women clinically diagno sed with interstitial cystitis according to National Institute for Dia betes and Digestive and Kidney Diseases criteria and 5 women diagnosed with urinary incontinence were used for immunohistochemical localizat ion of p65, an NF-kappa B subunit. Results: Our immunohistochemical lo calization experiments indicate that NF-KB was predominantly activated in bladder urothelial cells and cells of the submucosal layer in biop sies from patients with interstitial cystitis compared to controls. Wh ile activation was evident by intense nuclear localization of NF-kappa B in all interstitial cystitis specimens, diffuse and faint immunosta ining was observed in control samples. The results also indicate that activation of NF-kappa B correlated with disease occurrence. Conclusio ns: The fact that NF-kappa B is capable of transactivating pro-inflamm atory mediators, which in turn can amplify NF-kappa B activation by a positive regulatory loop, suggests that inflammatory and/or immune res ponses in interstitial cystitis can be exacerbated possibly by persist ent activation of this nuclear factor. We believe that our study provi des a novel basis for investigating the role of NF-kappa B activation in the pathophysiology of interstitial cystitis and further opens a fr ontier for the development of an innovative therapeutic approach to in terstitial cystitis.