Journal article
Succinate is an inflammatory signal that induces IL-1β through HIF-1α
GM Tannahill, AM Curtis, J Adamik, EM Palsson-Mcdermott, AF McGettrick, G Goel, C Frezza, NJ Bernard, B Kelly, NH Foley, L Zheng, A Gardet, Z Tong, SS Jany, SC Corr, M Haneklaus, BE Caffrey, K Pierce, S Walmsley, FC Beasley Show all
Nature | Published : 2013
DOI: 10.1038/nature11986
Abstract
Macrophages activated by the Gram-negative bacterial product lipopolysaccharide switch their core metabolism from oxidative phosphorylation to glycolysis. Here we show that inhibition of glycolysis with 2-deoxyglucose suppresses lipopolysaccharide-induced interleukin-1β but not tumour-necrosis factor-α in mouse macrophages. A comprehensive metabolic map of lipopolysaccharide-activated macrophages shows upregulation of glycolytic and downregulation of mitochondrial genes, which correlates directly with the expression profiles of altered metabolites. Lipopolysaccharide strongly increases the levels of the tricarboxylic-acid cycle intermediate succinate. Glutamine-dependent anerplerosis is the ..
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Awarded by Interleukin Foundation for Medical Research
Funding Acknowledgements
We thank the European Research Council, Science Foundation Ireland, the Health Research Board, European Union FP7 programme 'TIMER', Wellcome Trust, National Institutes of Health, Helmsley Trust, Nestle Research Centre, VESKI, The Duquesne University Hunkele Dreaded Disease Award, The Interleukin Foundation and the National Health and Medical Research Council for funding. We also thank R. Thompson for assistance with Hif1a<SUP>-/-</SUP> mice and M. Murphy for discussions.