Gliadin intake alters the small intestinal mucosa in indomethacin-treated HLA-DQ8 transgenic mice

Giuseppe Mazzarella, Paolo Bergamo, Francesco Maurano, Diomira Luongo, Vera Rotondi Aufiero, Giuseppina Bozzella, Gianna Palmieri, Riccardo Troncone, Salvatore Auricchio, Chella David, Mauro Rossi

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Celiac disease (CD) is an enteropathy caused by the ingestion of wheat gluten in genetically susceptible individuals. A complete understanding of the pathogenic mechanisms in CD has been hindered because of the lack of adequate in vivo models. In the present study, we explored the events after the intragastric administration of gliadin and of the albumin/ globulin fraction from wheat in human leukocyte antigen-DQ8 transgenic mice (DQ8 mice) treated with indomethacin, an inhibitor of cyclooxygenases (COXs). After 10 days of treatment, mice showed a significant reduction of villus height, increased crypt depth, increased number of lamina propria-activated macrophages, and high basal interferon-γ secretion in mesenteric lymph nodes, all of which were specifically related to gliadin intake, whereas the albumin/globulin fraction of wheat was unable to induce similar changes. Cotreatment with NS-398, a specific inhibitor of COX-2, also induced the intestinal lesion. Enteropathy onset was further characterized by high levels of oxidative stress markers, similar to CD. Biochemical assessment of the small intestine revealed the specific activation of matrix metalloproteinases 2 and 9, high caspase-3 activity, and a significant increase of tissue transglutaminase protein levels associated with the intestinal lesion. Notably, after 30 days of treatment, enteropathic mice developed serum antibodies toward gliadin (IgA) and tissue transglutaminase (IgG). We concluded that gliadin intake in combination with COX inhibition caused a basal inflammatory status and an oxidative stress condition in the small intestine of DQ8 mice, thus triggering the mucosal lesion and, subsequently, an antigen-specific immunity.

Original languageEnglish (US)
Pages (from-to)G302-G312
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume307
Issue number3
DOIs
StatePublished - 2014

Keywords

  • Cyclooxygenases
  • Enteropathy
  • Gliadin
  • Indomethacin
  • Transgenic mice

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

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    Mazzarella, G., Bergamo, P., Maurano, F., Luongo, D., Rotondi Aufiero, V., Bozzella, G., Palmieri, G., Troncone, R., Auricchio, S., David, C., & Rossi, M. (2014). Gliadin intake alters the small intestinal mucosa in indomethacin-treated HLA-DQ8 transgenic mice. American Journal of Physiology - Gastrointestinal and Liver Physiology, 307(3), G302-G312. https://doi.org/10.1152/ajpgi.00002.2014