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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Main Authors: Louisane Desbiens, Catherine Lapointe, Marjan Gharagozloo, Shaimaa Mahmoud, Gunnar Pejler, Denis Gris, Pedro D’Orléans-Juste
Format: Article
Language:English
Published: Wiley 2016-01-01
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
collection DOAJ
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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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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