Basic—Alimentary TractGliadin Induces an Increase in Intestinal Permeability and Zonulin Release by Binding to the Chemokine Receptor CXCR3
Section snippets
Reagents
Gliadin (crude wheat), pepsin, and trypsin were purchased from Sigma (St Louis, MO). Gliadin was pepsin/trypsin digested (PT-gliadin) as described previously10 with minor modifications.11 Recombinant α-gliadin was a gift from Dr D. Kasarda (USDA-ARS, Albany, CA). Recombinant interleukin (rIL)-1, monokine induced by interferon (IFN) γ (rMig/CXCL9), IFN-γ-inducible protein 10 (rIP-10/CXCL10), IFN-γ-inducible T-cell α-chemoattractant (rI-TAC/CXCL11), and tumor necrosis factor-α (rTNF-α) were
Identification of CXCR3 as the PT-Gliadin Intestinal Binding Protein
To identify the putative gliadin receptor, membrane fractions were prepared from rabbit small intestine and applied to an Affi-gel α-gliadin affinity column. Three main proteins with estimated molecular weights of 93, 100, and 107 kilodaltons were eluted from the affinity column and subjected to MALDI mass spectrometric fingerprint analysis following digestion with trypsin. The 100-kilodalton band was identified by mass spec/mass spec (MS/MS) as the chemokine receptor CXCR3, based on sequences
Discussion
TJs are central to the regulation of intestinal permeability because they maintain the contiguity of intestinal epithelial cells and are capable of prompt and coordinated responses to the many physiologic challenges to the intestinal epithelial barrier.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
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Supported in part by National Institutes of Health grants DK-48373 (to A.F.) and AI-18797 (to S.N.V.).
Conflicts of interest: S.N.V. and A.F. have financial relationship with Alba Therapeutics.