title: Time course of nitric oxide synthase generation after gluten exposure in the rectal mucosa of gluten-sensitive patients.
abstract: BACKGROUND
  Nitric oxide is thought to play an important role in modulating chronic inflammatory responses as well as in immune-mediated inflammation. We reproduced a gluten-mediated mucosal response in the rectum of celiac and control subjects in order to determine the role of inducible and constitutive nitric oxide synthases in the pathogenesis of this process.
  
  
  METHODS
  Nine patients with confirmed celiac disease and five healthy controls underwent a long-term rectal gluten challenge (48 h) after an enema of 6 g of crude gluten, and constitutive and inducible nitric oxide synthase activity were determined in rectal biopsies. The histological localization of inducible nitric oxide synthase was determined by immunohistochemistry.
  
  
  RESULTS
  Activity of both isoforms of nitric oxide synthase in control subjects did not change significantly after gluten instillation. In celiac patients, constitutive nitric oxide synthase on rectal mucosa also showed no significant changes after challenge with gluten. Inducible nitric oxide synthase isoform exhibited a modest increase 4 h after gluten instillation in celiac patients (mean increase 35% compared with baseline levels) but, 8 h after challenge, generation of iNO synthase was significantly higher: 54% more than pre-challenge production (P < 0.05) and higher than control values (P < 0.05). Inducible nitric oxide synthase staining was mostly localized in mononuclear cells of the epithelium and the lamina propria. After gluten instillation, the enhanced staining was mainly localized in subepithelial areas of the lamina propria.
  
  
  CONCLUSIONS
  Our data suggest a role for nitric oxide, generated by inducible nitric oxide synthase, in the process of rectal mucosa injury by local gluten instillation in sensitized patients. We could not, however, determine if the role of nitric oxide in the ensuing injury of this gluten-induced immune inflammation model is a protective one, or merely a by-product generated by the activation of the inflammatory cells.
authors.affiliation: Clinical Service, Hospital de Gastroenterologia, Universidad del Salvador, Buenos Aires, Argentina.
authors.forename: S
authors.initials: S
authors.lastname: Niveloni
authors.forename: S
authors.initials: S
authors.lastname: Weksler-Zangen
authors.forename: S
authors.initials: S
authors.lastname: Pedreira
authors.forename: R
authors.initials: R
authors.lastname: Dezi
authors.forename: E
authors.initials: E
authors.lastname: Granot
authors.forename: I
authors.initials: I
authors.lastname: Doldan
authors.forename: D
authors.initials: D
authors.lastname: Wengrower
authors.forename: H
authors.initials: H
authors.lastname: Vazquez
authors.forename: E
authors.initials: E
authors.lastname: Smecuol
authors.forename: J
authors.initials: J
authors.lastname: Valero
authors.forename: Z
authors.initials: Z
authors.lastname: Kogan
authors.forename: E
authors.initials: E
authors.lastname: Maurino
authors.forename: J C
authors.initials: JC
authors.lastname: Bai
authors.forename: E
authors.initials: E
authors.lastname: Goldin
mesh_terms: D000328:Adult; D002446:Celiac Disease / Q000201:enzymology*; D004733:Enema; D005260:Female; D005983:Glutens / Q000008:administration & dosage* / Q000494:pharmacology; D006801:Humans; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II; D012007:Rectum / Q000201:enzymology*; D013997:Time Factors
chemical_list: D005983:Glutens; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II