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Title: | Mast cells protect from post-traumatic spinal cord damage in mice by degrading inflammation-associated cytokines via mouse mast cell protease 4 | Authors: | NELISSEN, Sofie VANGANSEWINKEL, Tim GEURTS, Nathalie GEBOES, Lies LEMMENS, Evi VIDAL VERA, Pia LEMMENS, Stefanie WILLEMS, Leen Boato, Francesco DOOLEY, Dearbhaile Pehl, Debora Pejler, Gunnar Maurer, Marcus Metz, Martin HENDRIX, Sven |
Issue Date: | 2014 | Source: | NEUROBIOLOGY OF DISEASE, 62, p. 260-272 | Abstract: | Mast cells (MCs) are found abundantly in the central nervous system and play a complex role in neuroinflammatory diseases such as multiple sclerosis and stroke. In the present study,we show thatMC-deficient KitW-sh/W-sh mice display significantly increased astrogliosis and T cell infiltration as well as significantly reduced functional recovery after spinal cord injury compared to wildtype mice. In addition, MC-deficient mice show significantly increased levels of MCP-1, TNF-α, IL-10 and IL-13 protein levels in the spinal cord.Mice deficient inmouse mast cell protease 4 (mMCP4), an MC-specific chymase, also showed increased MCP-1, IL-6 and IL-13 protein levels in spinal cord samples and a decreased functional outcome after spinal cord injury. A degradation assay using supernatant from MCs derived from either mMCP4−/− mice or controls revealed that mMCP4 cleaves MCP-1, IL-6, and IL-13 suggesting a protective role for MC proteases in neuroinflammation. These data show for the first time that MCs may be protective after spinal cord injury and that they may reduce CNS damage by degrading inflammation-associated cytokines via the MC-specific chymasemMCP4. | Keywords: | mMCP4; mast cell; inflammation; spinal cord injury; MCP-1; TNF-α; IL-6; IL-10; IL-13 | Document URI: | http://hdl.handle.net/1942/16795 | ISSN: | 0969-9961 | e-ISSN: | 1095-953X | DOI: | 10.1016/j.nbd.2013.09.012 | ISI #: | 000330553600024 | Rights: | © 2013 The Authors. Published by Elsevier Inc. All rights reserved. Open access under CC BY license.Open access under CC BY license. | Category: | A1 | Type: | Journal Contribution | Validations: | ecoom 2015 |
Appears in Collections: | Research publications |
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nelissen 1.pdf | Published version | 1.63 MB | Adobe PDF | View/Open |
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