Children with celiac disease express inducible nitric oxide synthase in the small intestine during gluten challenge.
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.
Holmgren Peterson
K
K
Dept. of Medical Microbiology, Linköping University, Sweden.
Fälth-Magnusson
K
K
Magnusson
K E
KE
Stenhammar
L
L
Sundqvist
T
T
D000293:Adolescent; D002446:Celiac Disease / Q000201:enzymology*; D002675:Child, Preschool; D005983:Glutens / Q000494:pharmacology*; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007421:Intestine, Small / Q000201:enzymology*; D018613:Microscopy, Confocal; D009566:Nitrates / Q000652:urine; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000032:analysis*; D052247:Nitric Oxide Synthase Type II; D009573:Nitrites / Q000652:urine
D009566:Nitrates; D009573:Nitrites; D009569:Nitric Oxide; D005983:Glutens; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II