1. Humoral immune response to tissue transglutaminase is related to epithelial cell proliferation in celiac disease.
- Author
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Barone MV, Caputo I, Ribecco MT, Maglio M, Marzari R, Sblattero D, Troncone R, Auricchio S, and Esposito C
- Subjects
- Actins drug effects, Actins metabolism, Animals, Apoptosis immunology, Biopsy, Bromodeoxyuridine, Caco-2 Cells drug effects, Caco-2 Cells immunology, Caco-2 Cells pathology, Celiac Disease immunology, Celiac Disease pathology, Cell Cycle drug effects, Cell Cycle immunology, Epithelial Cells drug effects, Epithelial Cells immunology, GTP-Binding Proteins, Humans, In Situ Nick-End Labeling, Intestinal Mucosa drug effects, Intestinal Mucosa metabolism, Mice, NIH 3T3 Cells drug effects, NIH 3T3 Cells immunology, NIH 3T3 Cells pathology, Protein Glutamine gamma Glutamyltransferase 2, Recombinant Proteins, Antibody Formation drug effects, Autoantibodies therapeutic use, Celiac Disease drug therapy, Cell Proliferation drug effects, Epithelial Cells pathology, Intestinal Mucosa pathology, Transglutaminases immunology
- Abstract
Background & Aims: Tissue transglutaminase (tTG) autoantibodies are markers of celiac disease, and the enzyme is required for several crucial biological processes. The aim of this study was to determine whether these autoantibodies are involved in the pathogenesis of the mucosal lesion typical of celiac disease., Methods: Using rhodamine-conjugated phalloidin staining, we evaluated whether tTG antibodies, both commercially available and cloned from patients with celiac disease, cause cytoskeletal changes in Caco-2, MCF7, and NIH 3T3 cells. We monitored cell levels of bromodeoxyuridine incorporation to determine whether tTG autoantibodies are able to induce NIH 3T3 fibroblasts and epithelial mucosal cells into S phase., Results: Treatment with tTG antibodies caused a dose-dependent increase of membrane ruffling in Caco-2, MCF7, and NIH 3T3 cells. It also dose-dependently induced G(0)-synchronized NIH 3T3 fibroblasts into S phase but did not affect the rate of apoptosis. Similarly, tTG antibodies induced S-phase entry of epithelial cells in cultured intestinal biopsy specimens from patients with celiac disease. They did not affect biopsy specimens from patients without celiac disease., Conclusions: Our results suggest that tTG autoantibodies per se, by interacting with the extracellular membrane-bound transglutaminase, may play an important role in epithelial cell proliferation in celiac disease.
- Published
- 2007
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