Evidence map›Paper›PMID 27779186›Full record

ArticleNature communications2016

PKM2-dependent glycolysis promotes NLRP3 and AIM2 inflammasome activation.

Min Xie, Yan Yu, Rui Kang, Shan Zhu, Liangchun Yang, Ling Zeng, Xiaofang Sun, Minghua Yang, Timothy R Billiar, Haichao Wang and 3 more

Erratum issuedOpen access · goldAbstract read
In one paragraph

Article in Nature communications, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 323 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
323citing papers in PubMed, 1 pooled it
16.4field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

323 citing papers in PubMed, 1 synthesis or guideline pooled it, 552 citations in OpenAlex.

  1. Pooled it
  2. Dual metabolic checkpoint blockadeBioactive materials · 2027
    Article
  3. Article
  4. Review
  5. Review
  6. Review
  7. Article
  8. PKM2: A gatekeeper in macrophage metabolic reprogramming.Journal of pharmaceutical analysis · 2026
    Review
  9. Article
  10. Review
  11. Review
  12. Lactate acts as a metabolic brake on inflammation by repressing NLRP3 transcription via NF-κB inhibition.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026
    Article
  13. Review
  14. Article
  15. Article
  16. Article
  17. Review
  18. Article
  19. Caspase-1 in cancer and inflammatory diseases: a potential therapeutic target.Apoptosis : an international journal on programmed cell death · 2026
    Review
  20. Article

263 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

13 authors at 5 institutions in 2 countries.

Min XieDepartment of Pediatrics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
Yan YuDepartment of Pediatrics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
Rui KangDepartment of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania 15219, USA.
Shan ZhuCenter of DAMP Biology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510510, China.
Liangchun YangDepartment of Pediatrics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
Ling ZengDepartment of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania 15219, USA.
Xiaofang SunCenter of DAMP Biology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510510, China.
Minghua YangDepartment of Pediatrics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
Timothy R BilliarDepartment of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania 15219, USA.
Haichao WangLaboratory of Emergency Medicine, The Feinstein Institute for Medical Research, Manhasset, New York 11030, USA.ORCID 0000-0002-0211-9000
Lizhi CaoDepartment of Pediatrics, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China.
Jianxin JiangState Key Laboratory of Trauma, Burns and Combined Injury, Research Institute of Surgery, Research institute for Traffic Medicine of People's Liberation Army, Daping Hospital, Third Military Medical University, Chongqing 400042, China.
Daolin TangDepartment of Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania 15219, USA.
Central South University · CNUniversity of Pittsburgh · USArmy Medical University · CNThird Affiliated Hospital of Guangzhou Medical University · CNFeinstein Institute for Medical Research · US

Funding

Mechanisms of Novel Herbal Therapies for Sepsis.R01AT005076 · NCCIH · FEINSTEIN INSTITUTE FOR MEDICAL RESEARCH · PI WANG, HAICHAO · 2010 to 2023
$4.3M
Regulation of HMGB1 Release in Endotoxemia.R01GM063075 · NIGMS · NORTH SHORE UNIVERSITY HOSPITAL · PI WANG, HAICHAO · 2002 to 2020
$4.2M
Targeting HMGB1-mediated Autophagy in Cancer TherapyR01CA160417 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI TANG, DAOLIN · 2012 to 2023
$3.0M
NITRIC OXIDE AND HEPATIC FUNCTION IN SEPSIS AND TRAUMAR01GM044100 · NIGMS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI BILLIAR, TIMOTHY R · 1995 to 2017
$1.9M
Immunometabolism in SepsisR01GM115366 · NIGMS · UT SOUTHWESTERN MEDICAL CENTER · PI BILLIAR, TIMOTHY R, TANG, DAOLIN · 2015 to 2018
$1.2M
EPA EP-C-16-014NCCIH NIH HHS R01 AT005076NCI NIH HHS R01 CA160417NIGMS NIH HHS R01 GM044100NIGMS NIH HHS R01 GM063075NIGMS NIH HHS R01 GM115366
6 · The paper itself

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 PKM2-EIF2AK2 pathway protects mice from lethal endotoxemia and polymicrobial sepsis. Moreover, conditional knockout of PKM2 in myeloid cells protects mice from septic death induced by NLRP3 and AIM2 inflammasome activation. These findings define an important role of PKM2 in immunometabolism and guide future development of therapeutic strategies to treat sepsis.

Indexed as

AnimalsCarrier ProteinsCoinfectionDisease Models, AnimalDNA-Binding ProteinseIF-2 KinaseFemaleGlycolysisHMGB1 ProteinHumansInflammasomesInterleukin-18Interleukin-1betaMacrophagesMaleMembrane ProteinsAim2 protein, mouseCarrier ProteinsDNA-Binding ProteinseIF-2 KinaseHMGB1 ProteinHMGB1 protein, mouseIL1B protein, mouseInflammasomesInterleukin-18Interleukin-1betaMembrane ProteinsNaphthoquinonesNLR Family, Pyrin Domain-Containing 3 ProteinNlrp3 protein, mousePkm protein, mouseprotein kinase R, mousePyruvate KinaseshikoninThyroid Hormone-Binding ProteinsThyroid Hormones

Identifiers

PMID27779186
PMCPMC5093342
OpenAlexW2532112957

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.