Please use this identifier to cite or link to this item: 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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