P31-43 GLIADIN PEPTIDE ACTIVATES IN VIVO NLRP3 INFLAMMASOME

MICULÁN, EMANUEL ; PEREZ, FEDERICO; GOMEZ CASTRO, MARÍA FLORENCIA; CHIRDO, FERNANDO; RUERA, CAROLINA; CARASI PAULA

Mar del Plata

Congreso; SAIC-SAI-SAFE 2018; 2018

SAIC-SAI-SAFE

Celiac disease (CD) is a chronic enteropathy elicited by gluten peptides which produce a specific and strong Th1 response in small intestine . Using an in vivo murine model aimed to assess the initial stages in CD pathogenesis, we demonstrated that innate mechanisms are critical to drive mucosal changes (increase number of intraepithelial lymphocytes -IELs, and reduction in villus height /crypt depth (V/C) ratio) in proximal small intestine. Innate response was elicited by p31-43 gliadin peptide and our structural studies showed that this peptide forms oligomers. NLRP3 inflammasome may sense a broad range of stimuli including endogenous signals derived from damaged mitochondria by nanostructures.The aim of this work was to evaluate the role of NLRP3 inflammasome in the enteropathy induced by p31-43.C57BL/6 wild type, NLRP3 KO or CASP 1 KO mice were treated by intragastric administration of p31-43 or vehicle. Inhibition of caspase 1 activity was evaluated in C57BL/6 by i.p. administration of Ac-YVAD-cmk or vehicle. After 16h, intestinal samples were collected, and sections were H&E stained for histological evaluation. Protein extracts were used for westernblot (WB) analysis.WB analysis showed activation of caspase-1 and increased levels of IL-1β in small intestine of C57BL/6 mice intragastrically treated with p31-43 (p