Significant Contribution of Mouse Mast Cell Protease 4 in Early Phases of Experimental Autoimmune Encephalomyelitis
Experimental autoimmune encephalomyelitis (EAE) is a mouse model that reproduces cardinal signs of clinical, histopathological, and immunological features found in Multiple Sclerosis (MS). Mast cells are suggested to be involved in the main inflammatory phases occurring during EAE development, possi...
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Wiley
2016-01-01
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Series: | Mediators of Inflammation |
Online Access: | http://dx.doi.org/10.1155/2016/9797021 |
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author | Louisane Desbiens Catherine Lapointe Marjan Gharagozloo Shaimaa Mahmoud Gunnar Pejler Denis Gris Pedro D’Orléans-Juste |
author_facet | Louisane Desbiens Catherine Lapointe Marjan Gharagozloo Shaimaa Mahmoud Gunnar Pejler Denis Gris Pedro D’Orléans-Juste |
author_sort | Louisane Desbiens |
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description | Experimental autoimmune encephalomyelitis (EAE) is a mouse model that reproduces cardinal signs of clinical, histopathological, and immunological features found in Multiple Sclerosis (MS). Mast cells are suggested to be involved in the main inflammatory phases occurring during EAE development, possibly by secreting several autacoids and proteases. Among the latter, the chymase mouse mast cell protease 4 (mMCP-4) can contribute to the inflammatory response by producing endothelin-1 (ET-1). The aim of this study was to determine the impact of mMCP-4 on acute inflammatory stages in EAE. C57BL/6 wild type (WT) or mMCP-4 knockout (KO) mice were immunized with MOG35–55 plus complete Freund’s adjuvant followed by pertussis toxin. Immunized WT mice presented an initial acute phase characterized by progressive increases in clinical score, which were significantly reduced in mMCP-4 KO mice. In addition, higher levels of spinal myelin were found in mMCP-4 KO as compared with WT mice. Finally, whereas EAE triggered significant increases in brain levels of mMCP-4 mRNA and immunoreactive ET-1 in WT mice, the latter peptide was reduced to basal levels in mMCP-4 KO congeners. Together, the present study supports a role for mMCP-4 in the early inflammatory phases of the disease in a mouse model of MS. |
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language | English |
publishDate | 2016-01-01 |
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spelling | doaj-art-a57260e41af34b9bbdf956142e56cea02025-02-03T01:24:07ZengWileyMediators of Inflammation0962-93511466-18612016-01-01201610.1155/2016/97970219797021Significant Contribution of Mouse Mast Cell Protease 4 in Early Phases of Experimental Autoimmune EncephalomyelitisLouisane Desbiens0Catherine Lapointe1Marjan Gharagozloo2Shaimaa Mahmoud3Gunnar Pejler4Denis Gris5Pedro D’Orléans-Juste6Department of Pharmacology, Medical School, Université de Sherbrooke, 3001 12th Avenue North, Sherbrooke, QC, J1H 5N4, CanadaDepartment of Pharmacology, Medical School, Université de Sherbrooke, 3001 12th Avenue North, Sherbrooke, QC, J1H 5N4, CanadaDepartment of Pediatrics, Program of Immunology and Allergology, Medical School, Université de Sherbrooke, 3001 12th Avenue North, Sherbrooke, QC, J1H 5N4, CanadaDepartment of Pediatrics, Program of Immunology and Allergology, Medical School, Université de Sherbrooke, 3001 12th Avenue North, Sherbrooke, QC, J1H 5N4, CanadaDepartment of Medical Biochemistry and Microbiology, Uppsala University BMC, Box 582, 75123 Uppsala, SwedenDepartment of Pediatrics, Program of Immunology and Allergology, Medical School, Université de Sherbrooke, 3001 12th Avenue North, Sherbrooke, QC, J1H 5N4, CanadaDepartment of Pharmacology, Medical School, Université de Sherbrooke, 3001 12th Avenue North, Sherbrooke, QC, J1H 5N4, CanadaExperimental autoimmune encephalomyelitis (EAE) is a mouse model that reproduces cardinal signs of clinical, histopathological, and immunological features found in Multiple Sclerosis (MS). Mast cells are suggested to be involved in the main inflammatory phases occurring during EAE development, possibly by secreting several autacoids and proteases. Among the latter, the chymase mouse mast cell protease 4 (mMCP-4) can contribute to the inflammatory response by producing endothelin-1 (ET-1). The aim of this study was to determine the impact of mMCP-4 on acute inflammatory stages in EAE. C57BL/6 wild type (WT) or mMCP-4 knockout (KO) mice were immunized with MOG35–55 plus complete Freund’s adjuvant followed by pertussis toxin. Immunized WT mice presented an initial acute phase characterized by progressive increases in clinical score, which were significantly reduced in mMCP-4 KO mice. In addition, higher levels of spinal myelin were found in mMCP-4 KO as compared with WT mice. Finally, whereas EAE triggered significant increases in brain levels of mMCP-4 mRNA and immunoreactive ET-1 in WT mice, the latter peptide was reduced to basal levels in mMCP-4 KO congeners. Together, the present study supports a role for mMCP-4 in the early inflammatory phases of the disease in a mouse model of MS.http://dx.doi.org/10.1155/2016/9797021 |
spellingShingle | Louisane Desbiens Catherine Lapointe Marjan Gharagozloo Shaimaa Mahmoud Gunnar Pejler Denis Gris Pedro D’Orléans-Juste Significant Contribution of Mouse Mast Cell Protease 4 in Early Phases of Experimental Autoimmune Encephalomyelitis Mediators of Inflammation |
title | Significant Contribution of Mouse Mast Cell Protease 4 in Early Phases of Experimental Autoimmune Encephalomyelitis |
title_full | Significant Contribution of Mouse Mast Cell Protease 4 in Early Phases of Experimental Autoimmune Encephalomyelitis |
title_fullStr | Significant Contribution of Mouse Mast Cell Protease 4 in Early Phases of Experimental Autoimmune Encephalomyelitis |
title_full_unstemmed | Significant Contribution of Mouse Mast Cell Protease 4 in Early Phases of Experimental Autoimmune Encephalomyelitis |
title_short | Significant Contribution of Mouse Mast Cell Protease 4 in Early Phases of Experimental Autoimmune Encephalomyelitis |
title_sort | significant contribution of mouse mast cell protease 4 in early phases of experimental autoimmune encephalomyelitis |
url | http://dx.doi.org/10.1155/2016/9797021 |
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