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Children with celiac disease express inducible nitric oxide synthase in the small intestine during gluten challenge
K Holmgren Peterson1, K Fälth-Magnusson, K E Magnusson
1Dept. of Medical Microbiology, Linköping University, Sweden.
Insights
Children with active celiac disease show increased nitric oxide production in the small intestine, linked to higher urine nitrate/nitrite levels and inducible nitric oxide synthase (iNOS) expression. This may contribute to tissue injury.
Area of Science:
- Gastroenterology
- Immunology
- Pediatrics
Background:
- Childhood celiac disease affects 1 in 250 children in Sweden, representing a common chronic condition.
- Elevated urinary nitrate/nitrite in children with untreated celiac disease suggests increased nitric oxide (NO) production in inflamed intestinal mucosa.
- Nitric oxide synthase (NOS) enzymes, particularly inducible NOS (iNOS), produce NO from L-arginine and can be stimulated by inflammatory mediators.
Purpose of the Study:
- To investigate the source of elevated nitric oxide in the small intestine of children with active celiac disease.
- To determine if iNOS expression correlates with increased urinary nitrate/nitrite levels in pediatric celiac disease.
Main Methods:
- Small-intestinal biopsy specimens from children with active celiac disease and controls were analyzed.
- Immunohistochemistry using antibodies against iNOS was performed on biopsy specimens.
- Confocal microscopy was employed to visualize and assess iNOS labeling patterns.
Main Results:
- iNOS was detected in all seven biopsy specimens from children with elevated urinary nitrate/nitrite levels.
- iNOS was not detected in five out of six control specimens from children with normal urinary nitrate/nitrite levels.
- A clear correlation was observed between increased urinary nitrate/nitrite and iNOS expression in the small intestine.
Conclusions:
- Children with active celiac disease exhibit gluten-induced nitric oxide production in the small intestine.
- Increased iNOS expression in the intestine correlates with elevated urinary nitrate/nitrite levels in pediatric celiac disease.
- The elevated nitric oxide production is a potential contributor to small intestinal tissue injury in celiac disease.
Background:
Childhood celiac disease in Sweden is presently seen at an incidence of around 1/250 and is thus one of the commonest chronic diseases in children. It has recently been shown that children with untreated celiac disease have increased levels of nitrate/nitrite in the urine, most likely reflecting an increased production of nitric oxide in the inflamed mucosa. Nitric oxide is produced from L-arginine by an inducible or a constitutive nitric oxide synthase. The inducible nitric oxide synthase (iNOS) can be stimulated in various cells by, for instance, inflammatory mediators. The present study has been done to find a possible source of nitric oxide in the small intestine that could result in the increased levels of nitrate/nitrite in the urine in children with active celiac disease.
Methods:
Small-intestinal biopsy specimens from children with active celiac disease were labeled with rabbit-anti-human antibodies to iNOS and visualized with fluorescent pig anti-rabbit antibodies. The specimens were then analyzed with confocal microscopy to assess the labeling pattern.
Results:
In all of seven specimens from children with increased levels of nitrate/nitrite in the urine, we detected antibodies to iNOS, whereas in five of six control specimens--that is, from children with normal nitrate/nitrite levels--we could not detect any iNOS.
Conclusions:
Children with active celiac disease have a gluten-induced nitric oxide production in the small intestine reflected by increased urine levels of nitrate/nitrite and iNOS expression in the intestine. We conclude that the increased production of nitric oxide could presumably, directly or indirectly, result in injury of the small-intestinal tissue.