dc.contributor.author | MCGETTRICK-DILLON, ANNE | en |
dc.contributor.author | CORR, SINEAD | en |
dc.contributor.author | PALSSON, EVA | en |
dc.contributor.author | KELLY, VINCENT | en |
dc.contributor.author | O'NEILL, LUKE | en |
dc.date.accessioned | 2014-12-11T10:43:20Z | |
dc.date.available | 2014-12-11T10:43:20Z | |
dc.date.issued | 2013 | en |
dc.date.submitted | 2013 | en |
dc.identifier.citation | Tannahill, GM, Curtis, AM, Adamik, J, Palsson-McDermott, EM, McGettrick, AF, Goel, G, Frezza, C, Bernard, NJ, Kelly, B, Foley, NH, Zheng, L, Gardet, A, Tong, Z, Jany, SS, Corr, SC, Haneklaus, M, Caffrey, BE, Pierce, K, Walmsley, S, Beasley, FC, Cummins, E, Nizet, V, Whyte, M, Taylor, CT, Lin, H, Masters, SL, Gottlieb, E, Kelly, VP, Clish, C, Auron, PE, Xavier, RJ, O'Neill, LAJ, Succinate is an inflammatory signal that induces IL-1 beta through HIF-1 alpha, NATURE, 496, 7444, 2013, 238-+ | en |
dc.identifier.other | Y | en |
dc.identifier.uri | http://hdl.handle.net/2262/72421 | |
dc.description | PUBLISHED | en |
dc.description.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 principal source of succinate, although the 'GABA (γ-aminobutyric acid) shunt' pathway also has a role. Lipopolysaccharide-induced succinate stabilizes hypoxia-inducible factor-1α, an effect that is inhibited by 2-deoxyglucose, with interleukin-1β as an important target. Lipopolysaccharide also increases succinylation of several proteins. We therefore identify succinate as a metabolite in innate immune signalling, which enhances interleukin-1β production during inflammation. | en |
dc.description.sponsorship | The authors would like to thank S.F.I, the H.R.B, E.U. FP7 programme, Wellcome Trust, NIH, VESKI, N.H.M.R.C
and the E.R.C for funding. We also thank Roger Thompson, Department of Infection and Immunity, University of
Sheffield, for assistance with HIF-1
α
−/−
mice and Dr. Mike Murphy, Mitochondrial Biology Unit, Wellcome
Trust/MRC building, Cambridge, for helpful discussions | en |
dc.format.extent | 238-+ | en |
dc.language.iso | en | en |
dc.relation.ispartofseries | NATURE | en |
dc.relation.ispartofseries | 496 | en |
dc.relation.ispartofseries | 7444 | en |
dc.rights | Y | en |
dc.subject | tricarboxylic-acid cycle intermediate succinate | en |
dc.subject.lcsh | tricarboxylic-acid cycle intermediate succinate | en |
dc.title | Succinate is an inflammatory signal that induces IL-1 beta through HIF-1 alpha | en |
dc.type | Journal Article | en |
dc.type.supercollection | scholarly_publications | en |
dc.type.supercollection | refereed_publications | en |
dc.identifier.peoplefinderurl | http://people.tcd.ie/kellyvp | en |
dc.identifier.peoplefinderurl | http://people.tcd.ie/corrsc | en |
dc.identifier.peoplefinderurl | http://people.tcd.ie/laoneill | en |
dc.identifier.peoplefinderurl | http://people.tcd.ie/palssone | en |
dc.identifier.peoplefinderurl | http://people.tcd.ie/mcgettra | en |
dc.identifier.rssinternalid | 86694 | en |
dc.identifier.doi | http://dx.doi.org/10.1038/nature11986 | en |
dc.rights.ecaccessrights | openAccess | |
dc.subject.TCDTheme | Immunology, Inflammation & Infection | en |
dc.identifier.orcid_id | 0000-0001-7067-5407 | en |