ArticleThe Journal of biological chemistry2011
Cooperation of adenosine with macrophage Toll-4 receptor agonists leads to increased glycolytic flux through the enhanced expression of PFKFB3 gene.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 96 citations in OpenAlex.
- Review
- The flux of energy in critical illness and the obesity paradox.Physiological reviews · 2025Review
- The crucial role of metabolic reprogramming in driving macrophage conversion in kidney disease.Cellular & molecular biology letters · 2025Review
- HIF-1 regulates mitochondrial function in bone marrow-derived macrophages but not in tissue-resident alveolar macrophages.Scientific reports · 2025Article
- Metabolic reprogramming and interventions in angiogenesis.Journal of advanced research · 2025Review
- Phosphorylation of PFKL regulates metabolic reprogramming in macrophages following pattern recognition receptor activation.Nature communications · 2024Article
- Article
- Dysregulated cellular metabolism in atherosclerosis: mediators and therapeutic opportunities.Nature metabolism · 2024Review
- Inflammaging and fatty acid oxidation in monocytes and macrophages.Immunometabolism (Cobham, Surrey) · 2024Review
- Pathogenic role of PFKFB3 in endothelial inflammatory diseases.Frontiers in molecular biosciences · 2024Review
- Role of PFKFB3-driven glycolysis in sepsis.Annals of medicine · 2023Review
- Effects of glycolysis on the polarization and function of tumor‑associated macrophages (Review).International journal of oncology · 2023Review
- HDL and LDL have distinct, opposing effects on LPS-induced brain inflammation.Lipids in health and disease · 2023Article
- Overexpressed PKM2 promotes macrophage phagocytosis and atherosclerosis.Animal models and experimental medicine · 2023Article
- Hyperglycemia induces PFKFB3 overexpression and promotes malignant phenotype of breast cancer through RAS/MAPK activation.World journal of surgical oncology · 2023Article
- Augmented PFKFB3-mediated glycolysis by interferon-γ promotes inflammatory M1 polarization through the JAK2/STAT1 pathway in local vascular inflammation in Takayasu arteritis.Arthritis research & therapy · 2022Article
- Review
- The Contact Allergen NiSOFrontiers in immunology · 2021Article
- Hypoxia regulates GR function through multiple mechanisms involving microRNAs 103 and 107.Molecular and cellular endocrinology · 2020Article
- BCG Vaccinations Upregulate Myc, a Central Switch for Improved Glucose Metabolism in Diabetes.iScience · 2020Article
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Authors and funding
11 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Macrophages activated through Toll receptor triggering increase the expression of the A(2A) and A(2B) adenosine receptors. In this study, we show that adenosine receptor activation enhances LPS-induced pfkfb3 expression, resulting in an increase of the key glycolytic allosteric regulator fructose 2,6-bisphosphate and the glycolytic flux. Using shRNA and differential expression of A(2A) and A(2B) receptors, we demonstrate that the A(2A) receptor mediates, in part, the induction of pfkfb3 by LPS, whereas the A(2B) receptor, with lower adenosine affinity, cooperates when high adenosine levels are present. pfkfb3 promoter sequence deletion analysis, site-directed mutagenesis, and inhibition by shRNAs demonstrated that HIF1α is a key transcription factor driving pfkfb3 expression following macrophage activation by LPS, whereas synergic induction of pfkfb3 expression observed with the A(2) receptor agonists seems to depend on Sp1 activity. Furthermore, levels of phospho-AMP kinase also increase, arguing for increased PFKFB3 activity by phosphorylation in long term LPS-activated macrophages. Taken together, our results show that, in macrophages, endogenously generated adenosine cooperates with bacterial components to increase PFKFB3 isozyme activity, resulting in greater fructose 2,6-bisphosphate accumulation. This process enhances the glycolytic flux and favors ATP generation helping to develop and maintain the long term defensive and reparative functions of the macrophages.
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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.