Metabolite itaconate in host immunoregulation and defense

Yang W, Tao K, Zhang P, Chen X, Sun X, Li R. Maresin 1 protects against lipopolysaccharide/d-galactosamine-induced acute liver injury by inhibiting macrophage pyroptosis and inflammatory response. Biochem Pharmacol. 2022;195: 114863.

Article  CAS  PubMed  Google Scholar 

Gharavi AT, Hanjani NA, Movahed E, Doroudian M. The role of macrophage subtypes and exosomes in immunomodulation. Cell Mol Biol Lett. 2022;27:83.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Novakovic B, Habibi E, Wang SY, Arts RJW, Davar R, Megchelenbrink W, et al. β-glucan reverses the epigenetic state of LPS-induced immunological tolerance. Cell. 2016;167:1354-68.e14.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ju C, Ma Y, Zuo X, Wang X, Song Z, Zhang Z, et al. Photobiomodulation promotes spinal cord injury repair by inhibiting macrophage polarization through lncRNA TUG1-miR-1192/TLR3 axis. Cell Mol Biol Lett. 2023;28:5.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Edwards-Hicks J, Su H, Mangolini M, Yoneten KK, Wills J, Rodriguez-Blanco G, et al. MYC sensitises cells to apoptosis by driving energetic demand. Nat Commun. 2022;13:4674.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Chakraborty S, Balan M, Sabarwal A, Choueiri TK, Pal S. Metabolic reprogramming in renal cancer: events of a metabolic disease. Biochim Biophys Acta. 2021;1876: 188559.

CAS  Google Scholar 

Yang D, Peng M, Hou Y, Qin Y, Wan X, Zhu P, et al. Oxidized ATM promotes breast cancer stem cell enrichment through energy metabolism reprogram-mediated acetyl-CoA accumulation. Cell Death Dis. 2020;11:508.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Shi J, Cai C. Research progress on the mechanism of itaconate regulating macrophage immunometabolism. Front Immunol. 2022;13: 937247.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Peace CG, O’Neill LA. The role of itaconate in host defense and inflammation. J Clin Investig. 2022. https://doi.org/10.1172/JCI148548.

Article  PubMed  PubMed Central  Google Scholar 

Li R, Zhang P, Wang Y, Tao K. Itaconate: a metabolite regulates inflammation response and oxidative stress. Oxid Med Cell Longev. 2020;2020:5404780.

PubMed  PubMed Central  Google Scholar 

Ye DY, Noh MH, Moon JH, Milito A, Kim M, Lee JW, et al. Kinetic compartmentalization by unnatural reaction for itaconate production. Nat Commun. 2022;13:5353.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Shin JH, Yang JY, Jeon BY, Yoon YJ, Cho SN, Kang YH, et al. (1)H NMR-based metabolomic profiling in mice infected with Mycobacterium tuberculosis. J Proteome Res. 2011;10:2238–47.

Article  CAS  PubMed  Google Scholar 

Strelko CL, Lu W, Dufort FJ, Seyfried TN, Chiles TC, Rabinowitz JD, et al. Itaconic acid is a mammalian metabolite induced during macrophage activation. J Am Chem Soc. 2011;133:16386–9.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Michelucci A, Cordes T, Ghelfi J, Pailot A, Reiling N, Goldmann O, et al. Immune-responsive gene 1 protein links metabolism to immunity by catalyzing itaconic acid production. Proc Natl Acad Sci USA. 2013;110:7820–5.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zhu L, Chen L. Progress in research on paclitaxel and tumor immunotherapy. Cell Mol Biol Lett. 2019;24:40.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Bambouskova M, Gorvel L, Lampropoulou V, Sergushichev A, Loginicheva E, Johnson K, et al. Electrophilic properties of itaconate and derivatives regulate the IκBζ-ATF3 inflammatory axis. Nature. 2018;556:501–4.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Hooftman A, O’Neill LAJ. The immunomodulatory potential of the metabolite itaconate. Trends Immunol. 2019;40:687–98.

Article  CAS  PubMed  Google Scholar 

Li R, Yang W, Yin Y, Ma X, Zhang P, Tao K. 4-OI attenuates carbon tetrachloride-induced hepatic injury via regulating oxidative stress and the inflammatory response. Front Pharmacol. 2021;12: 651444.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zhao J, Guo S, Schrodi SJ, He D. Absent in melanoma 2 (AIM2) in rheumatoid arthritis: novel molecular insights and implications. Cell Mol Biol Lett. 2022;27:108.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lin J, Ren J, Gao DS, Dai Y, Yu L. The emerging application of itaconate: promising molecular targets and therapeutic opportunities. Front Chem. 2021;9: 669308.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Song X, Long D. Nrf2 and ferroptosis: a new research direction for neurodegenerative diseases. Front Neurosci. 2020;14:267.

Article  PubMed  PubMed Central  Google Scholar 

Swain A, Bambouskova M, Kim H, Andhey PS, Duncan D, Auclair K, et al. Comparative evaluation of itaconate and its derivatives reveals divergent inflammasome and type I interferon regulation in macrophages. Nat Metab. 2020;2:594–602.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Zhang Y, Zhou YJ, Tang JS, Lan JQ, Kang YY, Wu L, et al. A comparison study between dimethyl itaconate and dimethyl fumarate in electrophilicity, Nrf2 activation, and anti-inflammation in vitro. J Asian Nat Prod Res. 2022;24:577–88.

Article  CAS  PubMed  Google Scholar 

ElAzzouny M, Tom CT, Evans CR, Olson LL, Tanga MJ, Gallagher KA, et al. Dimethyl itaconate is not metabolized into itaconate intracellularly. J Biol Chem. 2017;292:4766–9.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Mills EL, Ryan DG, Prag HA, Dikovskaya D, Menon D, Zaslona Z, et al. Itaconate is an anti-inflammatory metabolite that activates Nrf2 via alkylation of KEAP1. Nature. 2018;556:113–7.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Hooftman A, Angiari S, Hester S, Corcoran SE, Runtsch MC, Ling C, et al. The immunomodulatory metabolite itaconate modifies NLRP3 and inhibits inflammasome activation. Cell Metab. 2020;32:468-78.e7.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Marrocco A, Frawley K, Pearce LL, Peterson J, O’Brien JP, Mullett SJ, et al. Metabolic adaptation of macrophages as mechanism of defense against crystalline silica. J Immunol. 2021;207:1627–40.

Article  CAS  PubMed  PubMed Central  Google Scholar 

He W, Henne A, Lauterbach M, Geißmar E, Nikolka F, Kho C, et al. Mesaconate is synthesized from itaconate and exerts immunomodulatory effects in macrophages. Nat Metab. 2022;4:524–33.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Chen F, Elgaher WAM, Winterhoff M, Büssow K, Waqas FH, Graner E, et al. Citraconate inhibits ACOD1 (IRG1) catalysis, reduces interferon responses and oxidative stress, and modulates inflammation and cell metabolism. Nat Metab. 2022;4:534–46.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Wolska A, Lech-Marańda E, Robak T. Toll-like receptors and their role in carcinogenesis and anti-tumor treatment. Cell Mol Biol Lett. 2009;14:248–72.

Article  CAS  PubMed  Google Scholar 

Degrandi D, Hoffmann R, Beuter-Gunia C, Pfeffer K. The proinflammatory cytokine-induced IRG1 protein associates with mitochondria. J Interferon Cytoki Res. 2009;29:55–67.

Article  CAS  Google Scholar 

Basler T, Jeckstadt S, Valentin-Weigand P, Goethe R. Mycobacterium paratuberculosis, Mycobacterium smegmatis, and lipopolysaccharide induce different transcriptional and post-transcriptional regulation of the IRG1 gene in murine macrophages. J Leukoc Biol. 2006;79:628–38.

Article  CAS  PubMed  Google Scholar 

Kim YJ, Kim JH, Lee KJ, Choi MM, Kim YH, Rhie GE, et al. Botulinum neurotoxin type A induces TLR2-mediated inflammatory responses in macrophages. PLoS ONE. 2015;10: e0120840.

Article  PubMed  PubMed Central  Google Scholar 

Kawai T, Takeuchi O, Fujita T, Inoue J, Mühlradt PF, Sato S, et al. Lipopolysaccharide stimulates the MyD88-independent pathway and results in activation of IFN-regulatory factor 3 and the expression of a subset of lipopolysaccharide-inducible genes. J Immunol. 2001;167:5887–94.

Article  CAS  PubMed 

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