mTORC1-Induced HK1-Dependent Glycolysis Regulates NLRP3 Inflammasome Activation.
mTORC1-Induced HK1-Dependent Glycolysis Regulates NLRP3 Inflammasome Activation.
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DOI：
10.1016/j.celrep.2015.05.046
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发表时间：
2015-07-07
期刊：
影响因子：
8.8
通讯作者：
Choi AMK
中科院分区：
文献类型：
--
作者：
Moon JS;Hisata S;Park MA;DeNicola GM;Ryter SW;Nakahira K;Choi AMK
哺乳动物雷帕霉素靶蛋白复合物1（mTORC 1）调节免疫细胞的活化和细胞能量代谢。虽然糖酵解与免疫功能有关，但糖酵解调节NLRP 3炎性小体激活的机制仍不清楚。在这里，我们证明了mTORC 1诱导的糖酵解为NLRP 3炎性小体激活提供了一个重要的机制。此外，我们证明了在mTORC 1的调节下，己糖激酶1（HK 1）依赖的糖酵解是NLRP 3炎性小体激活的关键代谢途径。通过抑制Raptor/mTORC 1或HK 1下调糖酵解抑制了巨噬细胞中响应于LPS和ATP的pro-IL-1 β成熟和caspase-1活化。这些结果表明，通过mTORC 1上调HK 1依赖性糖酵解调节NLRP 3炎性小体活化。
The mammalian target of rapamycin complex 1 (mTORC1) regulates activation of immune cells and cellular energy metabolism. While glycolysis has been linked to immune functions, the mechanisms by which glycolysis regulates NLRP3 inflammasome activation remain unclear. Here, we demonstrate that mTORC1-induced glycolysis provides an essential mechanism for NLRP3 inflammasome activation. Moreover, we demonstrate that hexokinase 1 (HK1)-dependent glycolysis, under the regulation of mTORC1, represents a critical metabolic pathway for NLRP3 inflammasome activation. Downregulation of glycolysis by inhibition of Raptor/mTORC1 or HK1 suppressed both pro-IL-1 β maturation and caspase-1 activation in macrophages in response to LPS and ATP. These results suggest that upregulation of HK1-dependent glycolysis by mTORC1 regulates NLRP3 inflammasome activation.