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http://hdl.handle.net/1942/16437
Title: | ADAM17 is a survival factor for microglial cells in vitro and in vivo after spinal cord injury in mice | Authors: | VIDAL VERA, Pia LEMMENS, Evi AVILA MACAYA, Ariel VANGANSEWINKEL, Tim Chalaris, A. Rose-John, S. HENDRIX, Sven |
Issue Date: | 2013 | Source: | CELL DEATH & DISEASE, 4(12), (ART N° e954) | Abstract: | A disintegrin and metalloprotease 17 (ADAM17) is a sheddase with important substrates including tumor necrosis factor-alpha (TNF-alpha) and its receptors, the p75 neurotrophin receptor (p75NTR), and members of the epidermal growth factor family. The rationale of this study was to inhibit ADAM17-induced shedding of soluble TNF-alpha in order to reduce detrimental inflammation after spinal cord injury (SCI). However, using the specific ADAM17 blocker BMS-561392 in neuronal and glial cell cultures, we show that proper functioning of ADAM17 is vital for oligodendrocyte and microglia survival in a p44 MAPK-dependent manner. In contrast, genetic ablation of ADAM17 specifically increases microglial death. Surprisingly, although blocking ADAM17 in vivo does not substantially change the ratio between membrane-bound and soluble TNF-alpha, it increases expression of the pro-apoptotic marker Bax and microglial apoptosis while impairing functional recovery after SCI. These data suggest that ADAM 17 is a key survival factor for microglial cells after SCI. | Notes: | Hendrix, S (reprint author), Hasselt Univ, Dept Morphol, Martelarenlaan 42, B-3500 Hasselt, Belgium. sven.hendrix@uhasselt.be | Keywords: | TACE; TNF-alpha; ERK; MAPK; apoptosis; macrophage/microglia | Document URI: | http://hdl.handle.net/1942/16437 | ISSN: | 2041-4889 | e-ISSN: | 2041-4889 | DOI: | 10.1038/cddis.2013.466 | ISI #: | 000329161300015 | Rights: | © 2013 Macmillan Publishers Limited All rights reserved. | Category: | A1 | Type: | Journal Contribution | Validations: | ecoom 2015 |
Appears in Collections: | Research publications |
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vidal 1.pdf | Published version | 3.44 MB | Adobe PDF | View/Open |
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