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 patholo...
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| Format: | Article |
| Language: | English |
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Wiley
2014-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2014/767185 |
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| author | Madonna R. Peter Mirjana Jerkic Valentin Sotov David N. Douda Daniela S. Ardelean Niousha Ghamami Flavia Lakschevitz Meraj A. Khan Susan J. Robertson Michael Glogauer Dana J. Philpott Nades Palaniyar Michelle Letarte |
| author_facet | Madonna R. Peter Mirjana Jerkic Valentin Sotov David N. Douda Daniela S. Ardelean Niousha Ghamami Flavia Lakschevitz Meraj A. Khan Susan J. Robertson Michael Glogauer Dana J. Philpott Nades Palaniyar Michelle Letarte |
| author_sort | Madonna R. Peter |
| collection | DOAJ |
| 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 | Article |
| id | doaj-art-344bf2cbeff046c28e604eb1f699f0e3 |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2014-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-344bf2cbeff046c28e604eb1f699f0e32025-02-03T06:11:10ZengWileyMediators of Inflammation0962-93511466-18612014-01-01201410.1155/2014/767185767185Impaired Resolution of Inflammation in the Endoglin Heterozygous Mouse Model of Chronic ColitisMadonna R. Peter0Mirjana Jerkic1Valentin Sotov2David N. Douda3Daniela S. Ardelean4Niousha Ghamami5Flavia Lakschevitz6Meraj A. Khan7Susan J. Robertson8Michael Glogauer9Dana J. Philpott10Nades Palaniyar11Michelle Letarte12Molecular Structure and Function Program, The Hospital for Sick Children, Toronto, ON, M5G 0A4, CanadaMolecular Structure and Function Program, The Hospital for Sick Children, Toronto, ON, M5G 0A4, CanadaMolecular Structure and Function Program, The Hospital for Sick Children, Toronto, ON, M5G 0A4, CanadaProgram in Physiology and Experimental Medicine, The Hospital for Sick Children, Toronto, ON, M5G 0A4, CanadaMolecular Structure and Function Program, The Hospital for Sick Children, Toronto, ON, M5G 0A4, CanadaMolecular Structure and Function Program, The Hospital for Sick Children, Toronto, ON, M5G 0A4, CanadaDepartment of Periodontology, Faculty of Dentistry, University of Toronto, Toronto, ON, M5G 1G6, CanadaProgram in Physiology and Experimental Medicine, The Hospital for Sick Children, Toronto, ON, M5G 0A4, CanadaDepartment of Immunology, University of Toronto, Toronto, ON, M5S 1A8, CanadaDepartment of Periodontology, Faculty of Dentistry, University of Toronto, Toronto, ON, M5G 1G6, CanadaDepartment of Immunology, University of Toronto, Toronto, ON, M5S 1A8, CanadaProgram in Physiology and Experimental Medicine, The Hospital for Sick Children, Toronto, ON, M5G 0A4, CanadaMolecular Structure and Function Program, The Hospital for Sick Children, Toronto, ON, M5G 0A4, CanadaEndoglin 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.http://dx.doi.org/10.1155/2014/767185 |
| spellingShingle | Madonna R. Peter Mirjana Jerkic Valentin Sotov David N. Douda Daniela S. Ardelean Niousha Ghamami Flavia Lakschevitz Meraj A. Khan Susan J. Robertson Michael Glogauer Dana J. Philpott Nades Palaniyar Michelle Letarte Impaired Resolution of Inflammation in the Endoglin Heterozygous Mouse Model of Chronic Colitis Mediators of Inflammation |
| 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 |
| url | http://dx.doi.org/10.1155/2014/767185 |
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