| Gliadin fragments promote migration of dendritic cells. | |
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MedLine Citation:
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PMID: 20406323 Owner: NLM Status: In-Data-Review |
Abstract/OtherAbstract:
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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 (PGE(2) ) 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 PGE(2) 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. |
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Authors:
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Barbara Chladkova; Jana Kamanova; Lenka Palova-Jelinkova; Jana Cinova; Peter Sebo; Ludmila Tuckova |
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Publication Detail:
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Type: Journal Article |
Journal Detail:
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Title: Journal of cellular and molecular medicine Volume: 15 ISSN: 1582-4934 ISO Abbreviation: J. Cell. Mol. Med. Publication Date: 2011 Apr |
Date Detail:
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Created Date: 2011-05-06 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101083777 Medline TA: J Cell Mol Med Country: England |
Other Details:
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Languages: eng Pagination: 938-48 Citation Subset: IM |
Copyright Information:
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© 2011 The Authors Journal of Cellular and Molecular Medicine © 2011 Foundation for Cellular and Molecular Medicine/Blackwell Publishing Ltd. |
Affiliation:
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Laboratory of Specific Cellular Immunity, Institute of Microbiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic Laboratory of Molecular Biology of Bacterial Pathogens, Institute of Microbiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic. |
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