Intraluminal administration of p31-43 gliadin peptide induces mucosal tissue damage in the small intestine

ARAYA R; RULLI E; CHIRDO F

Oslo

Congreso; 14th International Coeliac Disease Symposium; 2011

14th International Coeliac Disease Symposium

Intraluminal administration of p31-43 gliadin peptide induces mucosal tissue damage in the small intestine Araya R., Rulli E. and Chirdo F Objectives Coeliac disease (CD) is a chronic immune mediate enteropathy, in which both innate and adaptive mechanism play a role in the pathogenesis. There exists no animal model for the histological lesions observed in patients with active CD. It has been reported, however, that intraperitonealy (i.p.) injection of poly I:C (PIC) induces intestinal mucosal tissue damage. The aim of the present study was to develop a murine enteropathy model using innate immunity stimuli, such as PIC and the gliadin peptide p31-43. Methods C57BL/6J mice were inoculated intraperitonealy (i.p.) or into ligated loops with PIC, p31-43 or both, using an unrelated peptide as a control. Histology and RT-PCR analysis were performed on small intestine samples taken at 2, 12 and 72hs post inoculation. Results The injection of PIC into ligated loops resulted in histological changes of the intestinal mucosa after 12 and 72 hs post treatment. The structure of the intestinal villi was clearly disrupted, while crypt depth was unaffected. These changes were not observed in animals treated i.p. with PIC. The p31-43 induced similar changes and exacerbated the damage when administer together with PIC. No damage was found in animals treated with the unrelated peptide. The injection of PIC, p31-43 or the combination of both into ligated loops resulted in increased epithelial cell regeneration. The inoculation of PIC into ligated loops, but not i.p., induced the expression of IFNb and IL-15 in small intestine samples at 2 and 12hs post induction respectively. Conclusions Intraluminal administration of p31-43 induces severe enteropathy. Mucosal damage can be exacerbated when p31-43 is injected with PIC. This experimental model in genetically unmanipulated mice provides a useful tool to study early events of small intestine damage triggered by gliadin peptides.