Constitutive expression of inducible nitric oxide synthase in the mouse ileal mucosa

It has been demonstrated previously that the inducible isoform of nitric oxide synthase (iNOS) is present throughout the intestinal tract in various inflammatory disease processes. Here we demonstrate that iNOS mRNA is present in the ileum but not in the jejunum or colon of normal mice. By Western blot analysis, iNOS protein is also detected in normal ileum, but not in the normal jejunum. However, by 3 h postinjection of 0.5 mg/kg lipopolysaccharide (LPS), iNOS mRNA is also detectable in the jejunum and colon. The enzyme message and protein, localized immunohistochemically by in situ hybridization and iNOS expression, is normally restricted to the villus epithelial cells. The iNOS mRNA was also present in the ilea of mice with defined intestinal flora (anaerobes only), germ-free mice, nude mice, and to a lesser extent in mice with severe combined immunodeficiency. These results suggest that the constitutive presence of iNOS in ileal epithelium indicates a role for this enzyme in maintaining intestinal homeostasis.