ArticleMolecular medicine (Cambridge, Mass.)2013
Activation of AMPK enhances neutrophil chemotaxis and bacterial killing.
Article in Molecular medicine (Cambridge, Mass.), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 93 citations in OpenAlex.
- Emerging host-directed strategies for overcoming drug resistance and immune evasion in Staphylococcus aureus infections.Journal of advanced research · 2026Review
- Host-directed therapeutics against antimicrobial-resistant bacterial infections: emerging roles of multi-omics and systems biology.Frontiers in pharmacology · 2026Review
- The interplay between type 2 diabetes mellitus and sepsis: a scoping review.International journal of medical sciences · 2026Article
- The immunology of sepsis: translating new insights into clinical practice.Nature reviews. Nephrology · 2026Review
- Cepharanthine alleviates lipopolysaccharide-induced acute lung injury through modulating macrophage polarization.Scientific reports · 2025Article
- Extracellular vesicles from adipose-derived mesenchymal stem cells alleviate acute lung injury via the CBL/AMPK signaling pathway.BMC biology · 2025Article
- AMPK and CAMKK activation participate in early events ofFrontiers in veterinary science · 2025Article
- Metformin attenuates alveolar bone destruction in mice with apical periodontitis and inhibits pro-inflammatory cytokine synthesis in lipopolysaccharide-stimulated RAW264.7 through the AMPK-mTOR-NF-κB pathway.Frontiers in immunology · 2025Article
- The CAMKK/AMPK Pathway Contributes toInternational journal of molecular sciences · 2024Article
- Targeting AMP-activated protein kinase in sepsis.Frontiers in endocrinology · 2024Review
- Enhancing the anticancer potential of metformin: fabrication of efficient nanospanlastics,International journal of pharmaceutics: X · 2023Article
- AMPK activation improves recovery from pneumonia-induced lung injury via reduction of er-stress and apoptosis in alveolar epithelial cells.Respiratory research · 2023Article
- Cellular mechanisms underlying the impairment of macrophage efferocytosis.Immunology letters · 2023Review
- Toll-Like Receptor 4 (TLR4) and AMPK Relevance in Cardiovascular Disease.Advanced pharmaceutical bulletin · 2023Review
- Use of oral anti-diabetic drugs and risk of hospital and intensive care unit admissions for infections.The American journal of the medical sciences · 2022Article
- Metformin effect in models of inflammation is associated with activation of ATP-dependent potassium channels and inhibition of tumor necrosis factor-α production.Inflammopharmacology · 2022Article
- FJU-C28 inhibits the endotoxin-induced pro-inflammatory cytokines expression via suppressing JNK, p38 MAPK and NF-κB signaling pathways.Pharmacology research & perspectives · 2021Article
- A Novel Microfluidic Device for the Neutrophil Functional Phenotype Analysis: Effects of Glucose and Its Derivatives AGEs.Micromachines · 2021Article
- AMPK activates Parkin independent autophagy and improves post sepsis immune defense against secondary bacterial lung infections.Scientific reports · 2021Article
- Metformin Protects Myelin from Degeneration in A Mouse Model of Iysophosphatidylcholine-Induced Demyelination in The Optic Chiasm.Cell journal · 2021Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
An inability of neutrophils to eliminate invading microorganisms is frequently associated with severe infection and may contribute to the high mortality rates associated with sepsis. In the present studies, we examined whether metformin and other 5' adenosine monophosphate-activated protein kinase (AMPK) activators affect neutrophil motility, phagocytosis and bacterial killing. We found that activation of AMPK enhanced neutrophil chemotaxis in vitro and in vivo, and also counteracted the inhibition of chemotaxis induced by exposure of neutrophils to lipopolysaccharide (LPS). In contrast, small interfering RNA (siRNA)-mediated knockdown of AMPKα1 or blockade of AMPK activation through treatment of neutrophils with the AMPK inhibitor compound C diminished neutrophil chemotaxis. In addition to their effects on chemotaxis, treatment of neutrophils with metformin or aminoimidazole carboxamide ribonucleotide (AICAR) improved phagocytosis and bacterial killing, including more efficient eradication of bacteria in a mouse model of peritonitis-induced sepsis. Immunocytochemistry showed that, in contrast to LPS, metformin or AICAR induced robust actin polymerization and distinct formation of neutrophil leading edges. Although LPS diminished AMPK phosphorylation, metformin or AICAR was able to partially decrease the effects of LPS/toll-like receptor 4 (TLR4) engagement on downstream signaling events, particularly LPS-induced IκBα degradation. The IκB kinase (IKK) inhibitor PS-1145 diminished IκBα degradation and also prevented LPS-induced inhibition of chemotaxis. These results suggest that AMPK activation with clinically approved agents, such as metformin, may facilitate bacterial eradication in sepsis and other inflammatory conditions associated with inhibition of neutrophil activation and chemotaxis.
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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.