Itaconic acid is a mammalian metabolite induced during macrophage activation

Strelko, Cheryl L.; Lu, Wenyun; Dufort, Fay J.; Seyfried, Thomas N.; Chiles, Thomas C.; Rabinowitz, Joshua D.; Roberts, Mary F.

doi:10.1021/ja2070889

Cited by 391Immune cells in cancerMetabolomics and Mass Spectrometry StudiesMicrobial metabolism and enzyme function

Itaconic acid is a mammalian metabolite induced during macrophage activation

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Strelko, Cheryl L., Lu, Wenyun, Dufort, Fay J., Seyfried, Thomas N., Chiles, Thomas C., Rabinowitz, Joshua D., Roberts, Mary F.·2011·Journal of the American Chemical Society

DOI 10.1021/ja2070889PMC PMC3216473

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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.

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Synthesis of the antimicrobial metabolite itaconate is selectively up-regulated in mammalian immune cells under proinflammatory conditions.
“Recently, synthesis of the antimicrobial metabolite itaconate was identified in mammalian immune cells as being selectively up-regulated under proinflammatory conditions (19).”
From Immunoresponsive Gene 1 and Itaconate Inhibit Succinate Dehydrogenase to Modulate Intracellular Succinate Levels (2016) · cites this paper as [19]

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Authors: Strelko, C. L., Lu, W., Dufort, F. J., Seyfried, T. N., Chiles, T. C., Rabinowitz, J. D., & Roberts, M. F.
Affiliations: Boston College (US)
Princeton University (US)
Corresponding author: Roberts, Mary F.
ORCID: Lu, Wenyun
Seyfried, Thomas N.
Rabinowitz, Joshua D.
Roberts, Mary F.
Venue: Journal of the American Chemical Society
Publisher: American Chemical Society (ACS)
Published: 2011-09-27
Volume: 133
Issue: 41
Pages: 16386-16389
ISSN: 0002-7863 (ISSN-L)
1520-5126
DOI: 10.1021/ja2070889
PMC: PMC3216473
OpenAlex: W2011779154
Cited by: 391
References: 30
Citations by year: 2026: 43 · 2025: 41 · 2024: 44 · 2023: 38 · 2022: 44 · 2021: 41 · 2020: 37 · 2019: 32 · 2018: 24 · 2017: 8 · 2016: 19 · 2015: 8 · 2014: 7 · 2013: 4 · 2012: 1
FWCI: 1.70
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Journal of the American Chemical Society (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Cancer Institute (RC1CA147961)
Topics: Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Microbial metabolism and enzyme function
Keywords: itaconic acid, macrophage activation, cis-aconitate, TCA cycle metabolism, lipopolysaccharide, interferon-gamma, RAW 264.7 macrophages, immune response
MeSH terms: Animals, Interferon-gamma, Lipopolysaccharides, Macrophages, Succinates, Cell Line, Tumor, Mice

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Itaconic acid is a mammalian metabolite induced during macrophage activation

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