The physiological expression of inducible nitric oxide synthase (iNOS) in the human colon

Background-Inducible nitric oxide synthase (NOS) is expressed in the coloni c epithelium in both inflammatory bowel disease and colorectal cancer. Nitr ic oxide (NO), the product of this enzyme, has been implicated in the patho genesis of both conditions. However, there are conflicting data on whether iNOS is expressed in the normal, uninflamed human colon. Aims-To evaluate the expression of iNOS in histologically normal, non-infla med human colonic mucosa. Patients/Methods-Reverse transcription polymerase chain reaction (RT-PCR), immunoblotting, and immunohistochemistry were used to investigate the expre ssion of iNOS in 17 histologically normal specimens obtained at colectomy p erformed for colorectal neoplasia. In addition, 16 endoscopic mucosal biops ies, taken from normal individuals, were also evaluated. Eleven surgical sp ecimens and 16 endoscopic biopsies from patients with refractory ulcerative colitis were used as inflammatory controls. Results-All types of specimens expressed iNOS mRNA. Immunoblotting revealed a protein of approximately 130 kDa consistent with iNOS in mucosal extract s of 77% of normal individuals, and 85% of diseased controls. Immunolabelli ng localised this protein to the surface epithelium in most of the normal s pecimens and also to the crypt epithelium and inflammatory cells in the dis eased controls. Conclusions-These findings provide evidence that iNOS is often expressed in the surface epithelium of non-inflamed human colon, suggesting that it is induced by local luminal factors, such as bacterial lipopolysaccharide (end otoxin). The resultant NO produced at this site might act as an oxidative b arrier, reducing bacterial translocation and providing a means of defence a gainst pathogenic microorganisms.