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Celiac Disease Monocytes Induce a Barrier Defect in Intestinal Epithelial Cells

Intestinal epithelial barrier function in celiac disease (CeD) patients is altered. However, the mechanism underlying this effect is not fully understood. The aim of the current study was to evaluate the role of monocytes in eliciting the epithelial barrier defect in CeD. For this purpose, human mon...

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Autores principales: Delbue, Deborah, Cardoso-Silva, Danielle, Branchi, Federica, Itzlinger, Alice, Letizia, Marilena, Siegmund, Britta, Schumann, Michael
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6888450/
https://www.ncbi.nlm.nih.gov/pubmed/31717494
http://dx.doi.org/10.3390/ijms20225597
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author Delbue, Deborah
Cardoso-Silva, Danielle
Branchi, Federica
Itzlinger, Alice
Letizia, Marilena
Siegmund, Britta
Schumann, Michael
author_facet Delbue, Deborah
Cardoso-Silva, Danielle
Branchi, Federica
Itzlinger, Alice
Letizia, Marilena
Siegmund, Britta
Schumann, Michael
author_sort Delbue, Deborah
collection PubMed
description Intestinal epithelial barrier function in celiac disease (CeD) patients is altered. However, the mechanism underlying this effect is not fully understood. The aim of the current study was to evaluate the role of monocytes in eliciting the epithelial barrier defect in CeD. For this purpose, human monocytes were isolated from peripheral blood mononuclear cells (PBMCs) from active and inactive CeD patients and healthy controls. PBMCs were sorted for expression of CD14 and co-cultured with intestinal epithelial cells (IECs, Caco2BBe). Barrier function, as well as tight junctional alterations, were determined. Monocytes were characterized by profiling of cytokines and surface marker expression. Transepithelial resistance was found to be decreased only in IECs that had been exposed to celiac monocytes. In line with this, tight junctional alterations were found by confocal laser scanning microscopy and Western blotting of ZO-1, occludin, and claudin-5. Analysis of cytokine concentrations in monocyte supernatants revealed higher expression of interleukin-6 and MCP-1 in celiac monocytes. However, surface marker expression, as analyzed by FACS analysis after immunostaining, did not reveal significant alterations in celiac monocytes. In conclusion, CeD peripheral monocytes reveal an intrinsically elevated pro-inflammatory cytokine pattern that is associated with the potential of peripheral monocytes to affect barrier function by altering TJ composition.
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spelling pubmed-68884502019-12-09 Celiac Disease Monocytes Induce a Barrier Defect in Intestinal Epithelial Cells Delbue, Deborah Cardoso-Silva, Danielle Branchi, Federica Itzlinger, Alice Letizia, Marilena Siegmund, Britta Schumann, Michael Int J Mol Sci Article Intestinal epithelial barrier function in celiac disease (CeD) patients is altered. However, the mechanism underlying this effect is not fully understood. The aim of the current study was to evaluate the role of monocytes in eliciting the epithelial barrier defect in CeD. For this purpose, human monocytes were isolated from peripheral blood mononuclear cells (PBMCs) from active and inactive CeD patients and healthy controls. PBMCs were sorted for expression of CD14 and co-cultured with intestinal epithelial cells (IECs, Caco2BBe). Barrier function, as well as tight junctional alterations, were determined. Monocytes were characterized by profiling of cytokines and surface marker expression. Transepithelial resistance was found to be decreased only in IECs that had been exposed to celiac monocytes. In line with this, tight junctional alterations were found by confocal laser scanning microscopy and Western blotting of ZO-1, occludin, and claudin-5. Analysis of cytokine concentrations in monocyte supernatants revealed higher expression of interleukin-6 and MCP-1 in celiac monocytes. However, surface marker expression, as analyzed by FACS analysis after immunostaining, did not reveal significant alterations in celiac monocytes. In conclusion, CeD peripheral monocytes reveal an intrinsically elevated pro-inflammatory cytokine pattern that is associated with the potential of peripheral monocytes to affect barrier function by altering TJ composition. MDPI 2019-11-09 /pmc/articles/PMC6888450/ /pubmed/31717494 http://dx.doi.org/10.3390/ijms20225597 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Delbue, Deborah
Cardoso-Silva, Danielle
Branchi, Federica
Itzlinger, Alice
Letizia, Marilena
Siegmund, Britta
Schumann, Michael
Celiac Disease Monocytes Induce a Barrier Defect in Intestinal Epithelial Cells
title Celiac Disease Monocytes Induce a Barrier Defect in Intestinal Epithelial Cells
title_full Celiac Disease Monocytes Induce a Barrier Defect in Intestinal Epithelial Cells
title_fullStr Celiac Disease Monocytes Induce a Barrier Defect in Intestinal Epithelial Cells
title_full_unstemmed Celiac Disease Monocytes Induce a Barrier Defect in Intestinal Epithelial Cells
title_short Celiac Disease Monocytes Induce a Barrier Defect in Intestinal Epithelial Cells
title_sort celiac disease monocytes induce a barrier defect in intestinal epithelial cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6888450/
https://www.ncbi.nlm.nih.gov/pubmed/31717494
http://dx.doi.org/10.3390/ijms20225597
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