PKM2-dependent glycolysis promotes NLRP3 and AIM2 inflammasome activation
Central South University · Xiangya Hospital Central South University · +6 more institutions
Abstract
Sepsis, severe sepsis and septic shock are the main cause of mortality in non-cardiac intensive care units. Immunometabolism has been linked to sepsis; however, the precise mechanism by which metabolic reprogramming regulates the inflammatory response is unclear. Here we show that aerobic glycolysis contributes to sepsis by modulating inflammasome activation in macrophages. PKM2-mediated glycolysis promotes inflammasome activation by modulating EIF2AK2 phosphorylation in macrophages. Pharmacological and genetic inhibition of PKM2 or EIF2AK2 attenuates NLRP3 and AIM2 inflammasomes activation, and consequently suppresses the release of IL-1β, IL-18 and HMGB1 by macrophages. Pharmacological inhibition of the…
Citation impact
- FWCI
- 16.36
- Percentile
- 100%
- References
- 69
Authors
13- MXMin XieCorresponding
Central South University, Xiangya Hospital Central South University
- YYYan Yu
Central South University, University of Pittsburgh, Xiangya Hospital Central South University
- RKRui Kang
University of Pittsburgh
- SZShan Zhu
Third Affiliated Hospital of Guangzhou Medical University, Guangzhou Medical University
- LYLiangchun Yang
Central South University, Xiangya Hospital Central South University
Topics & keywords
- Inflammasome
- AIM2
- Sepsis
- PKM2
- Anaerobic glycolysis
- HMGB1
- Glycolysis
- Septic shock
- Good health and well-being
Funding
- UOUniversity of Pittsburgh
- NNNational Natural Science Foundation of China
- NSNatural Science Foundation of Guangdong ProvinceAwards: 31671435, RSG-16-014-01-CDD, R01CA160417, 2016A030308011, R01GM115366
- NINational Institutes of HealthAwards: R01GM115366, RSG-16-014-01-CDD, R01AT005076, R01CA160417, R01GM44100, 2016A030308011, 31671435, R01GM063075