Journal
NEUROBIOLOGY OF DISEASE
Volume 62, Issue -, Pages 260-272Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nbd.2013.09.012
Keywords
mMCP4; Mast cell; Inflammation; Spinal cord injury; MCP-1; TNF-alpha; IL-6; IL-10; IL-13
Categories
Funding
- Deutsche Forschungsgemeinschaft [SPP1394]
- Fonds Wetenschappelijk Onderzoek Vlaanderen (FWO) [G.0389.12, G0A5813]
- Agentschap voor Innovatie door Wetenschap en Technologie (IWT) [1.2.703.10N, 1.5.056.12N]
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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 that MC-deficient Kit(W-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-alpha, IL-10 and IL-13 protein levels in the spinal cord. Mice deficient in mouse 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 cytoldnes via the MC-specific chymase mMCP4. (C) 2013 The Authors. Published by Elsevier Inc All rights reserved.
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