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Humoral immune response to tissue transglutaminase is related to epithelial cell proliferation in celiac disease.
- Source :
-
Gastroenterology [Gastroenterology] 2007 Apr; Vol. 132 (4), pp. 1245-53. Date of Electronic Publication: 2007 Jan 21. - Publication Year :
- 2007
-
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.<br />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.<br />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.<br />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.
- 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
Subjects
Details
- Language :
- English
- ISSN :
- 0016-5085
- Volume :
- 132
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Gastroenterology
- Publication Type :
- Academic Journal
- Accession number :
- 17408665
- Full Text :
- https://doi.org/10.1053/j.gastro.2007.01.030