Gliadin-mediated proliferation and innate immune activation in XXXX are due to alterations in vesicular trafficking.

@entity1 @entity32 @entity1603 @entity1593 @entity470 @entity1373 @entity19757 @entity8252 @entity44262
BACKGROUND AND OBJECTIVES: Damage to intestinal mucosa in @entity1593 ( @entity1593 ) is mediated both by @entity32 due to adaptive and innate immune responses, with @entity8252 as a major mediator of the innate immune response, and by proliferation of crypt enterocytes as an early alteration of @entity1593 mucosa causing crypts @entity1373 . We have previously shown that gliadin peptide P31-43 induces proliferation of cell lines and celiac enterocytes by delaying degradation of the active @entity470 ( @entity470 ) due to delayed maturation of endocytic vesicles. @entity8252 is increased in the intestine of @entity1 affected by @entity1593 and has pleiotropic activity that ultimately results in immunoregulatory cross-talk between cells belonging to the innate and adaptive branches of the immune response. Aims of this study were to investigate the role of P31-43 in the induction of cellular proliferation and innate immune activation. METHODS/PRINCIPAL FINDINGS: Cell proliferation was evaluated by @entity1603 ( @entity1603 ) incorporation both in CaCo-2 cells and in biopsies from active @entity1593 cases and controls. We used real-time PCR to evaluate @entity8252 mRNA levels and FACS as well as ELISA and Western Blot (WB) analysis to measure protein levels and distribution in CaCo-2 cells. Gliadin and P31-43 induce a proliferation of both CaCo-2 cells and @entity1593 crypt enterocytes that is dependent on both @entity470 and @entity8252 activity. In CaCo-2 cells, P31-43 increased @entity8252 levels on the cell surface by altering intracellular trafficking. The increased @entity8252 protein was bound to IL15 receptor ( @entity44262 , did not require new protein synthesis and functioned as a growth factor. CONCLUSION: In this study, we have shown that P31-43 induces both increase of the trans-presented @entity8252 / @entity19757 complex on cell surfaces by altering the trafficking of the vesicular compartments as well as proliferation of crypt enterocytes with consequent remodelling of @entity1593 mucosa due to a cooperation of @entity8252 and @entity470 .
