Neniskyte Urte, Vilalta Anna, Brown Guy C
Department of Biochemistry, University of Cambridge, UK; Mouse Biology Unit, European Molecular Biology Laboratory, Italy.
Department of Biochemistry, University of Cambridge, UK.
FEBS Lett. 2014 Aug 25;588(17):2952-6. doi: 10.1016/j.febslet.2014.05.046. Epub 2014 Jun 6.
Tumour necrosis factor-α (TNF-α) is a pro-inflammatory cytokine, expressed in many brain pathologies and associated with neuronal loss. We show here that addition of TNF-α to neuronal-glial co-cultures increases microglial proliferation and phagocytosis, and results in neuronal loss that is prevented by eliminating microglia. Blocking microglial phagocytosis by inhibiting phagocytic vitronectin and P2Y6 receptors, or genetically removing opsonin MFG-E8, prevented TNF-α induced loss of live neurons. Thus TNF-α appears to induce neuronal loss via microglial activation and phagocytosis of neurons, causing neuronal death by phagoptosis.
肿瘤坏死因子-α（TNF-α）是一种促炎细胞因子，在许多脑部病变中表达，并与神经元丧失有关。我们在此表明，向神经元-神经胶质细胞共培养物中添加TNF-α会增加小胶质细胞的增殖和吞噬作用，并导致神经元丧失，而通过消除小胶质细胞可预防这种情况。通过抑制吞噬性玻连蛋白和P2Y6受体来阻断小胶质细胞吞噬作用，或通过基因手段去除调理素MFG-E8，可预防TNF-α诱导的活神经元丧失。因此，TNF-α似乎通过小胶质细胞活化和对神经元的吞噬作用诱导神经元丧失，通过吞噬凋亡导致神经元死亡。
