ArticleJournal of molecular cell biology2020
Pyruvate dehydrogenase kinase is a negative regulator of interleukin-10 production in macrophages.
Article in Journal of molecular cell biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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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.
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Who cites it
18 citing papers in PubMed, 32 citations in OpenAlex.
- Lactate metabolism and protein lactylation in colorectal cancer: from metabolic reprogramming to epigenetic regulation.Frontiers in oncology · 2026Review
- Histone lactylation: a new target for overcoming immune evasion and therapy resistance.Medical oncology (Northwood, London, England) · 2025Review
- Myocardial pyruvate dehydrogenase kinase 4 drives sex-specific cardiac responses to endotoxemia.JCI insight · 2025Article
- Targeting Lactate: An Emerging Strategy for Macrophage Regulation in Chronic Inflammation and Cancer.Biomolecules · 2024Review
- Harnessing metabolism of hepatic macrophages to aid liver regeneration.Cell death & disease · 2023Review
- The Role of Pyruvate Metabolism in Mitochondrial Quality Control and Inflammation.Molecules and cells · 2023Review
- Pyruvate Dehydrogenase Kinase 2 Accelerates Endotoxin Shock by Promoting Mitogen-Activated Protein Kinase Activation.Inflammation · 2023Article
- Mitochondrial dysfunctions in T cells: focus on inflammatory bowel disease.Frontiers in immunology · 2023Review
- Temporal changes in glucose metabolism reflect polarization in resident and monocyte-derived macrophages after myocardial infarction.Frontiers in cardiovascular medicine · 2023Article
- Contribution of Age, Brain Region, Mood Disorder Pathology, and Interindividual Factors on the Methylome of Human Microglia.Biological psychiatry · 2022Article
- Metabolism of tissue macrophages in homeostasis and pathology.Cellular & molecular immunology · 2022Review
- Metabolomic and lipidomic signatures associated with activation of human cDC1 (BDCA3Immunology · 2022Article
- Parity-induced changes to mammary epithelial cells control NKT cell expansion and mammary oncogenesis.Cell reports · 2021Article
- Acetyl-CoA Metabolism and Histone Acetylation in the Regulation of Aging and Lifespan.Antioxidants (Basel, Switzerland) · 2021Review
- Meta-Inflammation and Metabolic Reprogramming of Macrophages in Diabetes and Obesity: The Importance of Metabolites.Frontiers in immunology · 2021Review
- Pyruvate Dehydrogenase Kinase Inhibitor Dichloroacetate Improves Host Control ofFrontiers in immunology · 2021Article
- Molecular Subtypes of Oral Squamous Cell Carcinoma Based on Immunosuppression Genes Using a Deep Learning Approach.Frontiers in cell and developmental biology · 2021Article
- Understanding the molecular mechanisms of macrophage polarization and metabolic reprogramming in endometriosis: A narrative review.Reproductive medicine and biologyReview
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Interleukin-10 (IL-10) is the most potent anti-inflammatory cytokine in the body and plays an essential role in determining outcomes of many inflammatory diseases. Cellular metabolism is a critical determinant of immune cell function; however, it is currently unclear whether metabolic processes are specifically involved in IL-10 production. In this study, we aimed to find the central metabolic molecule regulating IL-10 production of macrophages, which are the main producers of IL-10. Transcriptomic analysis identified that metabolic changes were predominantly enriched in Kupffer cells at the early inflammatory phase of a mouse endotoxemia model. Among them, pyruvate dehydrogenase kinase (PDK)-dependent acute glycolysis was negatively involved in IL-10 production. Inhibition or knockdown of PDK selectively increased macrophage IL-10 expression. Mechanistically, PDK inhibition increased IL-10 production via profound phosphorylation of adenosine monophosphate (AMP)-activated protein kinase alpha 1 (AMPKα1) by restricting glucose uptake in lipopolysaccharide-stimulated macrophages. AMPKα1 consequently activated p38 mitogen-activated protein kinase, c-Jun N-terminal kinase, and cyclic AMP-responsive element-binding protein to regulate IL-10 production. Our study uncovers a previously unknown regulatory mechanism of IL-10 in activated macrophages involving an immunometabolic function of PDK.
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Registered trials
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.