Journal of cellular and molecular medicine, 2011-04, Vol.15 (4), p.938-948
2011
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Details
- Autor(en) / Beteiligte
- Titel
- Gliadin fragments promote migration of dendritic cells
- Ist Teil von
- Journal of cellular and molecular medicine, 2011-04, Vol.15 (4), p.938-948
- Ort / Verlag
- Oxford, UK: Blackwell Publishing Ltd
- Erscheinungsjahr
- 2011
- Quelle
- Wiley Blackwell Single Titles
- Beschreibungen/Notizen
- In genetically predisposed individuals, ingestion of wheat gliadin provokes a T‐cell‐mediated enteropathy, celiac disease. Gliadin fragments were previously reported to induce phenotypic maturation and Th1 cytokine production by human dendritic cells (DCs) and to boost their capacity to stimulate allogeneic T cells. Here, we monitor the effects of gliadin on migratory capacities of DCs. Using transwell assays, we show that gliadin peptic digest stimulates migration of human DCs and their chemotactic responsiveness to the lymph node‐homing chemokines CCL19 and CCL21. The gliadin‐induced migration is accompanied by extensive alterations of the cytoskeletal organization, with dissolution of adhesion structures, podosomes, as well as up‐regulation of the CC chemokine receptor (CCR) 7 on cell surface and induction of cyclooxygenase (COX)‐2 enzyme that mediates prostaglandin E2 (PGE2) production. Blocking experiments confirmed that gliadin‐induced migration is independent of the TLR4 signalling. Moreover, we showed that the α‐gliadin‐derived 31–43 peptide is an active migration‐inducing component of the digest. The migration promoted by gliadin fragments or the 31–43 peptide required activation of p38 mitogen‐activated protein kinase (MAPK). As revealed using p38 MAPK inhibitor SB203580, this was responsible for DC cytoskeletal transition, CCR7 up‐regulation and PGE2 production in particular. Taken together, this study provides a new insight into pathogenic features of gliadin fragments by demonstrating their ability to promote DC migration, which is a prerequisite for efficient priming of naive T cells, contributing to celiac disease pathology.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1582-1838eISSN: 1582-4934DOI: 10.1111/j.1582-4934.2010.01066.xTitel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3922678
- Format
- –
- Schlagworte
- Antigens, Celiac disease, Cell surface, Chemokine CCL19 - pharmacology, Chemokine CCL21 - pharmacology, Chemokine receptors, Chemokines, chemotaxis, Chemotaxis - drug effects, Chromatography, Cyclooxygenase 2 - metabolism, Cyclooxygenase-2, Cytoskeleton, Cytoskeleton - drug effects, Cytoskeleton - metabolism, dendritic cell, Dendritic cells, Dendritic Cells - cytology, Dendritic Cells - drug effects, Dendritic Cells - enzymology, Dinoprostone - biosynthesis, Enzyme Activation - drug effects, Gliadin, Gliadin - pharmacology, Homing behavior, Humans, Leukocyte migration, Ligands, Lymph nodes, Lymphocytes, Lymphocytes T, MAP kinase, MAP Kinase Signaling System - drug effects, Microscopy, migration, Models, Biological, p38 Mitogen-Activated Protein Kinases - metabolism, Pathogenesis, Penicillin, Peptide Fragments - pharmacology, Peptides, Prostaglandin E2, Prostaglandin endoperoxide synthase, Reagents, Receptors, CCR7 - metabolism, Small intestine, TLR4 protein, Toll-like receptors, Up-regulation, Up-Regulation - drug effects