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Nitric oxide and inflammatory bowel disease: evidence for local intestinal production in children with active colonic
J J Levine1, M J Pettei, E Valderrama
1Division of Gastroenterology and Nutrition, Schneider Children's Hospital, New Hyde Park, NY 11040, USA.
Insights
Children with active colitis show increased nitric oxide production, evidenced by higher stool and plasma nitrate + nitrite levels. Inducible nitric oxide synthase protein is found in intestinal epithelial cells during active inflammation.
Area of Science:
- Gastroenterology
- Molecular Biology
- Pediatric Inflammatory Bowel Disease
Background:
- Active colitis in inflammatory bowel disease (IBD) involves mucosal vasodilation, increased intestinal permeability, and abnormal colonic motility.
- Nitric oxide (NO) plays a key role in regulating local blood flow, vasomotor tone, and inflammation.
- Previous studies indicated increased NO production and inducible nitric oxide synthase (iNOS) activity in experimental colitis models.
Purpose of the Study:
- To investigate the relationship between NO production and colonic inflammation in children with active colitis.
- To compare NO production markers in children with IBD and healthy controls.
- To determine the presence and location of iNOS protein in the intestinal epithelium of children with active colitis.
Main Methods:
- Measurement of nitrate + nitrite levels in urine, stool, and plasma using the Griess assay.
- Immunohistochemical localization to determine the expression of iNOS protein in intestinal tissue.
Main Results:
- Urinary nitrate + nitrite levels did not differ significantly between patients and controls.
- Stool and plasma nitrate + nitrite concentrations were significantly higher in children with active colitis compared to controls (p < 0.05).
- Immunohistochemistry revealed iNOS protein exclusively within epithelial cells of colonic tissue from children with active colitis.
Conclusions:
- Active colonic inflammation in children is associated with increased nitric oxide production.
- Enhanced expression of iNOS protein in intestinal epithelial cells correlates with active colonic inflammation.
Background:
Active colitis in patients with inflammatory bowel disease is associated with mucosal vasodilation, increased intestinal permeability and abnormal colonic motility. Nitric oxide is a messenger molecule with many functions, including regulation of local blood flow, vasomotor tone, and inflammation. Increased nitric oxide production and inducible nitric oxide synthase activity have been demonstrated in experimental models of colitis. This study was designed to determine the relationship between nitric oxide production and colonic inflammation in children with active colitis and in control subjects and whether expression of inducible nitric oxide synthase protein is demonstrable in the intestinal epithelium of these patients.
Methods:
Nitrate + nitrite were measured in urine, stool, and plasma using the Griess assay. Expression of inducible nitric oxide synthase protein in intestinal tissue was determined by immunohistochemical localization.
Results:
Urinary nitrate + nitrite levels were not significantly different in patients and control subjects. In contrast, stool and plasma nitrate + nitrite concentrations were significantly higher in children with inflammatory bowel disease compared with levels in control children (stool: 162.4 +/- 31.0 mumol/l versus 77.2 +/- 22.1 mumol/l; plasma: 65.2 +/- 9.9 mumol/l versus 38.1 +/- 6.6 mumol/L; p < 0.05). Stool nitrate + nitrite levels significantly correlated with plasma values. Immunohistochemical staining of colonic tissue from children with inflammatory bowel disease demonstrated inducible nitric oxide synthase protein located exclusively in epithelial cells.
Conclusion:
Increased nitric oxide production and enhanced intestinal epithelial cell expression of inducible nitric oxide synthase protein are associated with active colonic inflammation.