Localization and expression of inducible nitric oxide synthase in biopsies from patients with interstitial cystitis.
OBJECTIVE
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.


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.
Department of Molecular Medicine and Surgery, Section of Urology, Karolinska Institutet, Stockholm, Sweden. lotta.renstrom-koskela@karolinska.se
L Renström
LR
Koskela
T
T
Thiel
I
I
Ehrén
P J
PJ
De Verdier
N P
NP
Wiklund
D000368:Aged; D015415:Biomarkers / Q000378:metabolism*; D001707:Biopsy, Needle; D015153:Blotting, Western; D018856:Cystitis, Interstitial / Q000201:enzymology* / Q000473:pathology* / Q000503:physiopathology; D018450:Disease Progression; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018570:Risk Assessment; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index
D015415:Biomarkers; D052247:Nitric Oxide Synthase Type II