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 antibod...

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Bibliographic Details
Published in:Biochimica et biophysica acta 2010-09, Vol.1802 (9), p.717-727
Main Authors: Caputo, Ivana, Barone, Maria Vittoria, Lepretti, Marilena, Martucciello, Stefania, Nista, Ivan, Troncone, Riccardo, Auricchio, Salvatore, Sblattero, Daniele, Esposito, Carla
Format: Article
Language:English
Subjects:
Anti-transglutaminase antibody
Autoantibodies - pharmacology
Caco-2 Cells
Celiac disease
Celiac Disease - immunology
Celiac Disease - metabolism
Drug Antagonism
Endocytosis
Endocytosis - drug effects
Endocytosis - immunology
Enzyme Activation - drug effects
Epithelial Cells - drug effects
Epithelial Cells - metabolism
Gliadin - chemistry
Gliadin - pharmacokinetics
Gliadin - pharmacology
Gliadin peptide
Humans
Intestinal Mucosa - drug effects
Intestinal Mucosa - metabolism
Peptide Fragments - chemistry
Peptide Fragments - pharmacokinetics
Peptide Fragments - pharmacology
S Phase - drug effects
Transglutaminase
Transglutaminases - antagonists & inhibitors
Transglutaminases - immunology
Transglutaminases - metabolism
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Summary: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.
ISSN:0925-4439
0006-3002
1879-260X
DOI:10.1016/j.bbadis.2010.05.010