Commitment to glycolysis sustains survival of NO-producing inflammatory dendritic cells
Commitment to glycolysis sustains survival of NO-producing inflammatory dendritic cells
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DOI：
10.1182/blood-2012-03-419747
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发表时间：
2012-08-16
期刊：
影响因子：
20.3
通讯作者：
Pearce, Edward J.
中科院分区：
文献类型：
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作者：
Everts, Bart;Amiel, Eyal;Pearce, Edward J.
TLR 激动剂在树突状细胞 (DC) 中启动快速激活程序，需要代谢和生物能量资源的支持。我们之前发现，TLR 信号传导促进有氧糖酵解和氧化磷酸化 (OXHPOS) 的下降，而葡萄糖限制会阻止激活并导致细胞过早死亡。然而，目前尚不清楚为什么在这种情况下 OXPHOS 会减少。在本研究中，我们利用实时代谢流分析表明，在表达诱导型 NO 合酶的炎症性血液单核细胞来源的 DC 中，TLR 激动剂激活后，线粒体活性逐渐丧失。我们发现这是因为 NO 抑制 OXPHOS，并且转向糖酵解是一种生存反应，当 OXPHOS 受到抑制时，它可以维持 ATP 水平。我们的数据表明，NO 是炎症性单核细胞衍生 DC 中的重要代谢调节剂。 （血。2012；120(7):1422-1431）
TLR agonists initiate a rapid activation program in dendritic cells (DCs) that requires support from metabolic and bioenergetic resources. We found previously that TLR signaling promotes aerobic glycolysis and a decline in oxidative phosphorylation (OXHPOS) and that glucose restriction prevents activation and leads to premature cell death. However, it remained unclear why the decrease in OXPHOS occurs under these circumstances. Using real-time metabolic flux analysis, in the present study, we show that mitochondrial activity is lost progressively after activation by TLR agonists in inflammatory blood monocyte-derived DCs that express inducible NO synthase. We found that this is because of inhibition of OXPHOS by NO and that the switch to glycolysis is a survival response that serves to maintain ATP levels when OXPHOS is inhibited. Our data identify NO as a profound metabolic regulator in inflammatory monocyte-derived DCs. (Blood. 2012;120(7):1422-1431)