ArticlePloS one2015
AMPK Activation by A-769662 Controls IL-6 Expression in Inflammatory Arthritis.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 49 citations in OpenAlex.
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- AMPK Signaling Pathway as a Potential Therapeutic Target for Parkinson's Disease.Advanced pharmaceutical bulletin · 2024Review
- Anti-Inflammatory Effects of Adiponectin Receptor Agonist AdipoRon against Intervertebral Disc Degeneration.International journal of molecular sciences · 2023Article
- Metabolic regulation of RA macrophages is distinct from RA fibroblasts and blockade of glycolysis alleviates inflammatory phenotype in both cell types.Cellular and molecular life sciences : CMLS · 2021Article
- Roles of AMPK and Its Downstream Signals in Pain Regulation.Life (Basel, Switzerland) · 2021Review
- The energy sensor AMPK orchestrates metabolic and translational adaptation in expanding T helper cells.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Therapeutic Applications of Type 2 Diabetes Mellitus Drug Metformin in Patients with Osteoarthritis.Pharmaceuticals (Basel, Switzerland) · 2021Review
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- Metabolic reprogramming as a key regulator in the pathogenesis of rheumatoid arthritis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2020Review
- Metformin: A Potential Therapeutic Tool for Rheumatologists.Pharmaceuticals (Basel, Switzerland) · 2020Review
- Metformin limits osteoarthritis development and progression through activation of AMPK signalling.Annals of the rheumatic diseases · 2020Article
- FGF21 Protects Dopaminergic Neurons in Parkinson's Disease Models Via Repression of Neuroinflammation.Neurotoxicity research · 2020Article
- Troponin destabilization impairs sarcomere-cytoskeleton interactions in iPSC-derived cardiomyocytes from dilated cardiomyopathy patients.Scientific reports · 2020Article
- Prkaa1 Metabolically Regulates Monocyte/Macrophage Recruitment and Viability in Diet-Induced Murine Metabolic Disorders.Frontiers in cell and developmental biology · 2020Article
- Pharmacological Characterization of the Microsomal Prostaglandin EFrontiers in pharmacology · 2020Article
- Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 2 countries.
Funding
Abstract
objectiveAMP-activated protein kinase (AMPK) is a serine/threonine protein kinase critically involved in the regulation of cellular energy homeostasis. It is a central regulator of both lipid and glucose metabolism. Many studies have suggested that AMPK activation exert significant anti-inflammatory and immunosuppressive effects. In this study, we assessed whether targeted activation of AMPK inhibits inflammatory arthritis in vivo.
methodsWe tested the effect of A-769662, a specific AMPK agonist (60mg/kg/bid) in mouse models of antigen-induced arthritis (AIA) and passive K/BxN serum-induced arthritis. The passive K/BxN serum-induced arthritis model was also applied to AMPKα1-deficient mice. Joints were harvested and subjected to histological analysis. IL-6 expression was measured in both joint tissues and sera by ELISA. The effect of A-769662 on bone marrow derived macrophage (BMDM) response to stimulation with TLR2 and TLR4 agonists was tested in vitro.
resultsAMPK activation by A-769662 reduced inflammatory infiltration and joint damage in both mouse models. IL-6 expression in serum and arthritic joints was significantly decreased in A-769662-treated mice. AMPKα1 deficient mice mildly elicited an increase of clinical arthritis. IL-6 expression at both mRNA and protein levels, phosphorylation of p65 NF-κB and MAPK phosphorylation were inhibited by A-769662 in BMDMs stimulated with either TLR2 or TLR4 agonists.
conclusionsAMPK activation by specific AMPK agonist A-769662 suppressed inflammatory arthritis in mice as well as IL-6 expression in serum and arthritic joints. These data suggest that targeted activation of AMPK has a potential to be an effective therapeutic strategy for IL-6 dependent inflammatory arthritis.
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