Gliadin, zonulin and gut permeability: Effects on celiac and non-celiac intestinal mucosa and intestinal cell lines

Abstract

Based on our results, we concluded that gliadin activates zonulin signaling irrespective of the genetic expression of autoimmunity, leading to increased intestinal permeability to macromolecules.

Gliadin Induces an Increase in Intestinal Permeability and Zonulin Release by Binding to the Chemokine Receptor CXCR3

“…4 Increased intestinal permeability appears to be an early biologic change that precedes the onset of autoimmune diseases, including CD and type I diabetes. 8,23,24 The peculiarity of CD is that it is the only autoimmune disease for which the triggering environmental factor gliadin is known. This offers a unique opportunity to study the cellular and molecular basis of the autoimmune process using enzymatically digested gliadin as a stimulus in experimental assays.…”

“…8 Intestinal tissues of wild-type C57BL/6 and CXCR3 −/− mice were mounted in microsnapwell chambers, and PT-gliadin was added to the mucosal (eg, apical) side of the tissue. No differences in intestinal mucosal morphology or baseline TEER were noted between C57BL/6 and CXCR3 −/− mice (data not shown).…”

“…6 Furthermore, ex vivo studies, using intestinal biopsy specimens in the microsnapwell system, showed that intestinal biopsy specimens of CD patients mounted a more pronounced response to gliadin when compared with nonceliac controls, including an increased and persistent release of zonulin and a significant increase in intestinal permeability. 8 It is noteworthy that epithelial release of zonulin occurs after apical, but not basolateral, exposure to gliadin. 9 The latter finding implies that gliadin interacts with an intestinal luminal receptor and prompted us to seek the identity of this moiety.…”

Early tissue transglutaminase–mediated response underlies K562(S)-cell gliadin-dependent agglutination

“…Changes in cytoskeleton organization upon external triggers, such as gliadin or "toxic" gliadin peptides, may activate either intracellular pathways or external signaling events responsible for cell-to-cell communication, interaction, or movements. Cell contact could in turn impact intracellular events and cell differentiation, as described in confluent intestinal epithelial cell lines (27). The confluence of cells cultured in a Petri dish may be considered the prototype of movements in a two-dimensional space.…”

Overexpression of Hsp70 confers cytoprotection during gliadin exposure in Caco-2 cells

“…The pathological lesion is histologically characterized by a flattened small intestinal mucosa, caused by villous atrophy and crypt cell hyperplasia, with a lymphocytic infiltrate as well as a modification of cellular morphology and increased epithelial cell proliferation. These alterations reduce mucosal integrity (4)(5)(6). Clinically, this injury results in diarrhea and in malabsorption.…”