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Significant Contribution of Mouse Mast Cell Protease 4 in Early Phases of Experimental Autoimmune Encephalomyelitis
Univ Sherbrooke, Sch Med, Dept Pharmacol, 3001 12th Ave North, Sherbrooke, PQ J1H 5N4, Canada..
Univ Sherbrooke, Sch Med, Dept Pharmacol, 3001 12th Ave North, Sherbrooke, PQ J1H 5N4, Canada..
Univ Sherbrooke, Sch Med, Dept Pediat, Program Immunol & Allergol, 3001 12th Ave North, Sherbrooke, PQ J1H 5N4, Canada..
Univ Sherbrooke, Sch Med, Dept Pediat, Program Immunol & Allergol, 3001 12th Ave North, Sherbrooke, PQ J1H 5N4, Canada..
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2016 (English)In: Mediators of Inflammation, ISSN 0962-9351, E-ISSN 1466-1861, 9797021Article in journal (Refereed) Published
Abstract [en]

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 MOG(35-55) 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 form MCP-4 in the early inflammatory phases of the disease in a mouse model of MS.

Place, publisher, year, edition, pages
2016. 9797021
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Immunology in the medical area
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URN: urn:nbn:se:uu:diva-303410DOI: 10.1155/2016/9797021ISI: 000382064400001OAI: oai:DiVA.org:uu-303410DiVA: diva2:971727
Available from: 2016-09-19 Created: 2016-09-19 Last updated: 2016-09-19Bibliographically approved

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Pejler, Gunnar
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