title: Itaconic acid is a mammalian metabolite induced during macrophage activation.
abstract: Itaconic acid (ITA), or methylenesuccinic acid, is not generally classified as a mammalian metabolite. Using NMR-based metabolomics and (13)C-labeling, we have detected ITA in both macrophage-like VM-M3 and RAW 264.7 tumor cell lines as well as stimulated and unstimulated primary murine macrophages. Macrophage activation by addition of lipopolysaccharide and IFN-γ markedly increased ITA production and secretion. Crude cell extracts synthesize ITA via decarboxylation of cis-aconitate, indicative of a novel mammalian cis-aconitic decarboxylase activity. Our results highlight a previously unidentified biosynthetic pathway related to TCA cycle metabolism in mammalian cells and a novel metabolite that likely plays a role in macrophage-based immune response.
authors.affiliation: Department of Chemistry, Boston College, Chestnut Hill, Massachusetts 02467, USA.
authors.forename: Cheryl L
authors.initials: CL
authors.lastname: Strelko
authors.forename: Wenyun
authors.initials: W
authors.lastname: Lu
authors.forename: Fay J
authors.initials: FJ
authors.lastname: Dufort
authors.forename: Thomas N
authors.initials: TN
authors.lastname: Seyfried
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Chiles
authors.forename: Joshua D
authors.initials: JD
authors.lastname: Rabinowitz
authors.forename: Mary F
authors.initials: MF
authors.lastname: Roberts
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D013386:Succinates / Q000032:analysis / Q000378:metabolism*
chemical_list: D008070:Lipopolysaccharides; D013386:Succinates; D007371:Interferon-gamma; C005229:itaconic acid