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Cited by 95Inflammasome and immune disordersImmune Response and InflammationAdenosine and Purinergic Signaling

ATP-Induced Inflammasome Activation and Pyroptosis Is Regulated by AMP-Activated Protein Kinase in Macrophages

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Zha, Qing-Bing, Wei, Hong-Xia, Li, Chen-Guang, Liang, Yi-Dan, Xu, Li-Hui, Bai, Wen-Jing, Pan, Hao, He, Xian-Hui +1 more·2016·Frontiers in Immunology
DOI 10.3389/fimmu.2016.00597PMC PMC5149551
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Abstract

ATP is released by bacteria and host cells during bacterial infection as well as sterile tissue injury, acting as an inducer of inflammasome activation. Previous studies have shown that ATP treatment leads to AMP-activated protein kinase (AMPK) activation. However, it is unclear whether AMPK signaling has been involved in the regulation of ATP-induced inflammasome activation and subsequent pyroptosis. In this study, we aimed to investigate this issue in lipopolysaccharide-activated murine macrophages. Our results showed that AMPK signaling was activated in murine macrophages upon ATP treatment, which was accompanied by inflammasome activation and pyroptosis as evidenced by rapid cell membrane rupture as well as mature interleukin (IL)-1β and active caspase-1p10 release. The ATP-induced inflammasome activation and pyroptosis were markedly suppressed by an AMPK inhibitor compound C or small interfering RNA-mediated knockdown of AMPKα, but could be greatly enhanced by metformin (a well-known AMPK agonist). Importantly, metformin administration increased the mortality of mice with bacterial sepsis, which was likely because metformin treatment enhanced the systemic inflammasome activation as indicated by elevated serum and hepatic IL-1β levels. Collectively, these data indicated that the AMPK signaling positively regulated ATP-induced inflammasome activation and pyroptosis in macrophages, highlighting the possibility of AMPK-targeting therapies for inflammatory diseases involving inflammasome activation.

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  • iMG have lower baseline activation compared with immortalized microglia like HMC3 and were significantly more activated upon LPS treatment followed by ATP.

    “We discovered that iMG have lower baseline activation as compared with immortalized microglia like HMC3 and were significantly more activated upon LPS treatment followed by ATP, which facilitates NLRP3 inflammasome assembly (Supplementary Figure S2).55”

    From Tubular human brain organoids to model microglia-mediated neuroinflammation (2021) · cites this paper as [55]

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Authors
Zha, Q.-B., Wei, H.-X., Li, C.-G., Liang, Y.-D., Xu, L.-H., Bai, W.-J., Pan, H., He, X.-H., & Ouyang, D.-Y.
Affiliations
Jinan University (CN)
Corresponding author
Ouyang, Dong-Yun
ORCID
Venue
Frontiers in Immunology
Publisher
Frontiers Media SA
Published
2016-12-12
Volume
7
Pages
597-597
ISSN
1664-3224 (ISSN-L)
DOI
10.3389/fimmu.2016.00597
PMC
PMC5149551
OpenAlex
W2567141944
Cited by
95
References
4
Citations by year
2026: 6 · 2025: 8 · 2024: 14 · 2023: 5 · 2022: 14 · 2021: 15 · 2020: 8 · 2019: 11 · 2018: 8 · 2017: 6
FWCI
4.33
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Frontiers in Immunology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
National Natural Science Foundation of China (81673664, 81173604, 81373423)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Inflammasome and immune disorders
  • Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Adenosine and Purinergic Signaling
Keywords
ATP, inflammasome activation, pyroptosis, AMPK, macrophages, metformin, caspase-1, IL-1β, bacterial sepsis, lipopolysaccharide, compound C, inflammatory diseases

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