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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2019
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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. |
format | Online Article Text |
id | pubmed-6888450 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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