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Impaired Resolution of Inflammation in the Endoglin Heterozygous Mouse Model of Chronic Colitis
Endoglin is a coreceptor of the TGF-β superfamily predominantly expressed on the vascular endothelium and selective subsets of immune cells. We previously demonstrated that Endoglin heterozygous (Eng (+/−)) mice subjected to dextran sulfate sodium (DSS) developed persistent gut inflammation and path...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi Publishing Corporation
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4121192/ https://www.ncbi.nlm.nih.gov/pubmed/25114380 http://dx.doi.org/10.1155/2014/767185 |
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author | Peter, Madonna R. Jerkic, Mirjana Sotov, Valentin Douda, David N. Ardelean, Daniela S. Ghamami, Niousha Lakschevitz, Flavia Khan, Meraj A. Robertson, Susan J. Glogauer, Michael Philpott, Dana J. Palaniyar, Nades Letarte, Michelle |
author_facet | Peter, Madonna R. Jerkic, Mirjana Sotov, Valentin Douda, David N. Ardelean, Daniela S. Ghamami, Niousha Lakschevitz, Flavia Khan, Meraj A. Robertson, Susan J. Glogauer, Michael Philpott, Dana J. Palaniyar, Nades Letarte, Michelle |
author_sort | Peter, Madonna R. |
collection | PubMed |
description | Endoglin is a coreceptor of the TGF-β superfamily predominantly expressed on the vascular endothelium and selective subsets of immune cells. We previously demonstrated that Endoglin heterozygous (Eng (+/−)) mice subjected to dextran sulfate sodium (DSS) developed persistent gut inflammation and pathological angiogenesis. We now report that colitic Eng (+/−) mice have low colonic levels of active TGF-β1, which was associated with reduced expression of thrombospondin-1, an angiostatic factor known to activate TGF-β1. We also demonstrate dysregulated expression of BMPER and follistatin, which are extracellular regulators of the TGF-β superfamily that modulate angiogenesis and inflammation. Heightened colonic levels of the neutrophil chemoattractant and proangiogenic factor, CXCL1, were also observed in DSS-treated Eng (+/−) mice. Interestingly, despite increased macrophage and neutrophil infiltration, a gut-specific reduction in expression of the key phagocytic respiratory burst enzymes, NADPH oxidase 2 (Nox-2) and myeloperoxidase, was seen in Eng (+/−) mice undergoing persistent inflammation. Taken together, these findings suggest that endoglin is required for TGF-β superfamily mediated resolution of inflammation and fully functional myeloid cells. |
format | Online Article Text |
id | pubmed-4121192 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Hindawi Publishing Corporation |
record_format | MEDLINE/PubMed |
spelling | pubmed-41211922014-08-11 Impaired Resolution of Inflammation in the Endoglin Heterozygous Mouse Model of Chronic Colitis Peter, Madonna R. Jerkic, Mirjana Sotov, Valentin Douda, David N. Ardelean, Daniela S. Ghamami, Niousha Lakschevitz, Flavia Khan, Meraj A. Robertson, Susan J. Glogauer, Michael Philpott, Dana J. Palaniyar, Nades Letarte, Michelle Mediators Inflamm Research Article Endoglin is a coreceptor of the TGF-β superfamily predominantly expressed on the vascular endothelium and selective subsets of immune cells. We previously demonstrated that Endoglin heterozygous (Eng (+/−)) mice subjected to dextran sulfate sodium (DSS) developed persistent gut inflammation and pathological angiogenesis. We now report that colitic Eng (+/−) mice have low colonic levels of active TGF-β1, which was associated with reduced expression of thrombospondin-1, an angiostatic factor known to activate TGF-β1. We also demonstrate dysregulated expression of BMPER and follistatin, which are extracellular regulators of the TGF-β superfamily that modulate angiogenesis and inflammation. Heightened colonic levels of the neutrophil chemoattractant and proangiogenic factor, CXCL1, were also observed in DSS-treated Eng (+/−) mice. Interestingly, despite increased macrophage and neutrophil infiltration, a gut-specific reduction in expression of the key phagocytic respiratory burst enzymes, NADPH oxidase 2 (Nox-2) and myeloperoxidase, was seen in Eng (+/−) mice undergoing persistent inflammation. Taken together, these findings suggest that endoglin is required for TGF-β superfamily mediated resolution of inflammation and fully functional myeloid cells. Hindawi Publishing Corporation 2014 2014-07-10 /pmc/articles/PMC4121192/ /pubmed/25114380 http://dx.doi.org/10.1155/2014/767185 Text en Copyright © 2014 Madonna R. Peter et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Peter, Madonna R. Jerkic, Mirjana Sotov, Valentin Douda, David N. Ardelean, Daniela S. Ghamami, Niousha Lakschevitz, Flavia Khan, Meraj A. Robertson, Susan J. Glogauer, Michael Philpott, Dana J. Palaniyar, Nades Letarte, Michelle Impaired Resolution of Inflammation in the Endoglin Heterozygous Mouse Model of Chronic Colitis |
title | Impaired Resolution of Inflammation in the Endoglin Heterozygous Mouse Model of Chronic Colitis |
title_full | Impaired Resolution of Inflammation in the Endoglin Heterozygous Mouse Model of Chronic Colitis |
title_fullStr | Impaired Resolution of Inflammation in the Endoglin Heterozygous Mouse Model of Chronic Colitis |
title_full_unstemmed | Impaired Resolution of Inflammation in the Endoglin Heterozygous Mouse Model of Chronic Colitis |
title_short | Impaired Resolution of Inflammation in the Endoglin Heterozygous Mouse Model of Chronic Colitis |
title_sort | impaired resolution of inflammation in the endoglin heterozygous mouse model of chronic colitis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4121192/ https://www.ncbi.nlm.nih.gov/pubmed/25114380 http://dx.doi.org/10.1155/2014/767185 |
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