ADAM17 is a survival factor for microglial cells in vitro and in vivo after spinal cord injury in mice.

摘要: A disintegrin and metalloprotease 17 (ADAM17) is a sheddase with important substrates including tumor necrosis factor-α (TNF-α) its receptors, the p75 neurotrophin receptor (p75NTR), members of epidermal growth factor family. The rationale this study was to inhibit ADAM17-induced shedding soluble TNF-α in order reduce detrimental inflammation after spinal cord injury (SCI). However, using specific ADAM17 blocker BMS-561392 neuronal glial cell cultures, we show that proper functioning vital for oligodendrocyte microglia survival p44 MAPK-dependent manner. In contrast, genetic ablation specifically increases microglial death. Surprisingly, although blocking vivo does not substantially change ratio between membrane-bound TNF-α, it expression pro-apoptotic marker Bax apoptosis while impairing functional recovery SCI. These data suggest key cells