INVESTIGATIVE UROLOGY

Localization and expression of inducible nitric oxide synthase in biopsies from patients with interstitial cystitis
Koskela LR, Thiel T, Ehrén I, De Verdier PJ, Wiklund NP
Department of Molecular Medicine and Surgery, Section of Urology, Karolinska Institutet, Stockholm, Sweden
J Urol. 2008; 180: 737-41

• Purpose: Interstitial cystitis is a chronic inflammatory disease of the bladder and luminal nitric oxide has been shown to be increased in the bladder in patients with interstitial cystitis. We analyzed endogenous nitric oxide formation and inducible nitric oxide synthase gene expression in the bladder of patients with interstitial cystitis to obtain further knowledge of the localization of inducible nitric oxide synthase in the bladder mucosa.
• Materials and Methods: Six patients with interstitial cystitis and 8 controls were studied. In these 2 groups endogenous nitric oxide formation was measured and inducible nitric oxide synthase expression in bladder biopsies was analyzed at the transcriptional and protein levels by real-time polymerase chain reaction and Western blot, respectively. Immunohistochemistry for inducible nitric oxide synthase was also performed.
• Results: Patients with interstitial cystitis had higher inducible nitric oxide synthase mRNA expression and nitric oxide formation than controls (p <0.01 and <0.001, respectively). Inducible nitric oxide synthase protein expression was up-regulated in the interstitial cystitis group. Immunohistochemistry showed that inducible nitric oxide synthase was predominantly localized to the urothelium in patients with interstitial cystitis but inducible nitric oxide synthase-like immunoreactivity was also found in macrophages in the bladder mucosa.
• Conclusions: The increased levels of endogenously formed nitric oxide in patients with interstitial cystitis correspond to increased inducible nitric oxide synthase mRNA expression and protein levels in these patients. Furthermore, inducible nitric oxide synthase was found to be localized to the urothelium but it was also found in macrophages in the bladder mucosa. Whether high levels of endogenously formed nitric oxide are a part of the pathogenesis in interstitial cystitis and whether it has a protective or damaging role remain to be elucidated.
  
  
• Editorial Comment
  Analyzing patients with interstitial cystitis (IC) and controls, the authors evaluated whether high levels of endogenous nitric oxide (NO) in the bladder in patients with IC also correspond to increased levels of iNOS at a transcriptional and protein level. Also, the authors studied the location of iNOS in the bladder mucosa.
  It was found that the bladder luminal NO concentration was significantly increased in patients with IC when compared to controls. At the transcriptional level iNOS expression was detectable in biopsies from patients with IC as well as in controls. However, iNOS mRNA expression was significantly higher in biopsies from patients with IC when compared to controls. In addition, iNOS protein expression was found in the biopsies of patients with IC but not in the biopsies of controls.
  This important study opens new avenue for understanding the pathophysiology of IC and also for additional diagnostic tools of this until now under understanding disease.

Dr. Francisco J. B. Sampaio
Full-Professor and Chair, Urogenital Research Unit
State University of Rio de Janeiro
Rio de Janeiro, RJ, Brazil
E-mail: sampaio@urogenitalresearch.org