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Subject = tricarboxylic-acid cycle intermediate succinate;
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Succinate is an inflammatory signal that induces IL-1 beta through HIF-1 alpha
(2013)
MCGETTRICK-DILLON, ANNE; CORR, SINEAD; PALSSON, EVA; KELLY, VINCENT; O'NEILL, LUKE
Succinate is an inflammatory signal that induces IL-1 beta through HIF-1 alpha
(2013)
MCGETTRICK-DILLON, ANNE; CORR, SINEAD; PALSSON, EVA; KELLY, VINCENT; O'NEILL, LUKE
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-1? but not tumour-necrosis factor-? 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 (?-aminobutyric acid) shunt' pathway also has a role. Lipopolysaccharide-induced succinate stabilizes hypoxia-inducible factor-1?, an effect that is inhibited by 2-deoxyglucose, with interleukin-1? as an important target. Lipopolysacchar...
http://hdl.handle.net/2262/72421
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