Celiac anti-tissue transglutaminase antibodies interfere with the uptake of alpha gliadin peptide 31-43 but not of peptide 57-68 by epithelial cells.
Celiac disease is characterized by the secretion of IgA-class autoantibodies that target tissue transglutaminase (tTG). It is now recognized that anti-tTG antibodies are functional and not mere bystanders in the pathogenesis of celiac disease. Here we report that interaction between anti-tTG antibodies and extracellular membrane-bound tTG inhibits peptide 31-43 (but not peptide 57-68) uptake by cells, thereby impairing the ability of p31-43 to drive Caco-2 cells into S-phase. This effect did not involve tTG catalytic activity. Because anti-tTG antibodies interfered with epidermal growth factor endocytosis, we assume that they exert their effect by reducing peptide 31-43 endocytosis. Our results suggest that cell-surface tTG plays a hitherto unknown role in the regulation of gliadin peptide uptake and endocytosis.
Caputo
Ivana
I
Department of Chemistry, University of Salerno, Italy.
Barone
Maria Vittoria
MV
Lepretti
Marilena
M
Martucciello
Stefania
S
Nista
Ivan
I
Troncone
Riccardo
R
Auricchio
Salvatore
S
Sblattero
Daniele
D
Esposito
Carla
C
D001323:Autoantibodies / Q000494:pharmacology*; D018938:Caco-2 Cells; D002446:Celiac Disease / Q000276:immunology* / Q000378:metabolism; D004336:Drug Antagonism; D004705:Endocytosis / Q000187:drug effects / Q000276:immunology; D004789:Enzyme Activation / Q000187:drug effects; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D005903:Gliadin / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D010446:Peptide Fragments / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D016196:S Phase / Q000187:drug effects; D011503:Transglutaminases / Q000037:antagonists & inhibitors* / Q000276:immunology* / Q000378:metabolism
D001323:Autoantibodies; D010446:Peptide Fragments; C553138:gliadin peptide (31-43); C553139:gliadin peptide (57-68); D005903:Gliadin; D011503:Transglutaminases