ArticleAmerican journal of physiology. Lung cellular and molecular physiology2014
GSK3β-dependent inhibition of AMPK potentiates activation of neutrophils and macrophages and enhances severity of acute lung injury.
Article in American journal of physiology. Lung cellular and molecular physiology, 2014. 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, 89 citations in OpenAlex.
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- PAK4 in metabolic diseases: regulation by nutrient signals and therapeutic implications.Experimental & molecular medicine · 2026Review
- CD11b-modified ROS/pH-responsive nanoparticles co-deliver Dioscin and siRNA to improve cardiac repair after myocardial infarction by reducing neutrophil recruitment.Materials today. Bio · 2025Article
- Innate immune response in acute critical illness: a narrative review.Annals of intensive care · 2024Review
- PAK4 phosphorylates and inhibits AMPKα to control glucose uptake.Nature communications · 2024Article
- Ac2-26 activated the AKT1/GSK3β pathway to reduce cerebral neurons pyroptosis and improve cerebral function in rats after cardiopulmonary bypass.BMC cardiovascular disorders · 2024Article
- Glycogen Synthase Kinase-3 Inhibition by CHIR99021 Promotes Alveolar Epithelial Cell Proliferation and Lung Regeneration in the Lipopolysaccharide-Induced Acute Lung Injury Mouse Model.International journal of molecular sciences · 2024Article
- AMPK activation improves recovery from pneumonia-induced lung injury via reduction of er-stress and apoptosis in alveolar epithelial cells.Respiratory research · 2023Article
- Metformin Use Is Associated With Lower Mortality in Veterans With Diabetes Hospitalized With Pneumonia.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2023Article
- Liang-Ge-San: a classic traditional Chinese medicine formula, attenuates acute inflammation via targeting GSK3β.Frontiers in pharmacology · 2023Article
- Redox regulation of the immune response.Cellular & molecular immunology · 2022Review
- Glycogen synthesis and beyond, a comprehensive review of GSK3 as a key regulator of metabolic pathways and a therapeutic target for treating metabolic diseases.Medicinal research reviews · 2022Review
- E3 Ligase FBXW7 FacilitatesFrontiers in cellular and infection microbiology · 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
- Metformin: Experimental and Clinical Evidence for a Potential Role in Emphysema Treatment.American journal of respiratory and critical care medicine · 2021Observational
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- Inhibition of cell proliferation and promotion of acinus-like structure formation from goat mammary epithelial cells via Wnt/β-catenin signaling.In vitro cellular & developmental biology. Animal · 2021Article
- miR‑205‑3p promotes lung cancer progression by targeting APBB2.Molecular medicine reports · 2021Article
- AMPK activates Parkin independent autophagy and improves post sepsis immune defense against secondary bacterial lung infections.Scientific reports · 2021Article
- Oximes: Novel Therapeutics with Anticancer and Anti-Inflammatory Potential.Biomolecules · 2021Review
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Although AMP-activated protein kinase (AMPK) is involved in regulating carbohydrate and lipid metabolism, activated AMPK also plays an anti-inflammatory role in many cell populations. However, despite the ability of AMPK activation to diminish the severity of inflammatory responses, previous studies have found that AMPK activity is diminished in LPS-treated neutrophils and also in lungs of mice with LPS-induced acute lung injury (ALI). Since GSK3β participates in regulating AMPK activity, we examined potential roles for GSK3β in modulating LPS-induced activation of neutrophils and macrophages and in influencing severity of ALI. We found that GSK3β-dependent phosphorylation of T479-AMPK was associated with pT172 dephosphorylation and inactivation of AMPK following TLR4 engagement. GSK3β inhibitors BIO (6-bromoindirubin-3'-oxime), SB216763, or siRNA knockdown of GSK3β, but not the PI3K/AKT inhibitor LY294002, prevented Thr172-AMPK dephosphorylation. Exposure to LPS resulted in rapid binding between IKKβ and AMPKα, and phosphorylation of S485-AMPK by IKKβ. These results suggest that IKKβ-dependent phosphorylation of S485-AMPK was an essential step in subsequent phosphorylation and inactivation AMPK by GSK3β. Inhibition of GSK3β activity delayed IκBα degradation and diminished expression of the proinflammatory TNF-α in LPS-stimulated neutrophils and macrophages. In vivo, inhibition of GSK3β decreased the severity of LPS-induced lung injury as assessed by development of pulmonary edema, production of TNF-α and MIP-2, and release of the alarmins HMGB1 and histone 3 in the lungs. These results show that inhibition of AMPK by GSK3β plays an important contributory role in enhancing LPS-induced inflammatory responses, including worsening the severity of ALI.
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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.