Self-assembly properties may be linked to the in vivo effects of p31-43 gliadin peptide

MICULÁN, EMANUEL; GÓMEZ CASTRO, MARÍA FLORENCIA; HERRERA, MARÍA GEORGINA; CAROLINA N. RUERA; FEDERICO PEREZ; PRIETO, EDUARDO DANIEL; BARRERA, EXEQUIEL; PANTANO, SERGIO; CARASI, PAULA; CHIRDO FERNANDO

Urbino

Encuentro; 33rd Meeting of the WGPAT; 2019

European Prolamin Working Group of Prolamin Analysis and Toxicity

Celiac disease (CD) is a chronic enteropathy elicited by a Th1 response to glutenpeptides in the small intestine of genetically susceptible individuals. However, itremains unclear what drives the induction of inflammatory responses against harmlessantigens in food. By studying the biological properties of the p31-43 peptide (p31-43)from α-gliadin, we observed the induction of mucosal damage and innate immuneresponse in the proximal small intestine upon intragastric p31-43 administration inwild type mice. By in vivo studies, we demonstrated that mucosal damage triggered byp31-43 requires the NLRP3 inflammasome (NLRP3, ASC and caspase 1). Asconsequence of inflammasome activation we observed production of IL-1β.Administration of p31-43, but not scrambled or inverted peptides, to normal miceinduced histological changes in the proximal small intestine (reduction of Villusheight/Crypt depth ratio, and increase in IEL number). Since a cellular receptor forp31-43 has not been identified, this raises the question of how this peptide couldmediate different biological effects. With the aim to characterise the conformation ofp31-43 different biophysical and in silico tools were used. Dynamic Light Scattering(DLS) and Atomic Force Microscopy (AFM) analysis showed p31-43 oligomers withdifferent height distribution. By Circular Dichroism, we observed that p31-43 selforganized in a poly-proline II conformation in equilibrium with β-sheets-likestructures, which remained stable in the pH range of 3 to 8. In addition, these findingswere supported by Molecular Dynamics Simulation. The formation of p31-43oligomers may help to explain the molecular etiopathogenesis in the induction of proinflammatory effects and subsequent damage at the intestinal mucosa in CD.