Itaconate is an anti-inflammatory metabolite that activates Nrf2 via alkylation of KEAP1
Open accessAbstract
The endogenous metabolite itaconate has recently emerged as a regulator of macrophage function, but its precise mechanism of action remains poorly understood. Here we show that itaconate is required for the activation of the anti-inflammatory transcription factor Nrf2 (also known as NFE2L2) by lipopolysaccharide in mouse and human macrophages. We find that itaconate directly modifies proteins via alkylation of cysteine residues. Itaconate alkylates cysteine residues 151, 257, 288, 273 and 297 on the protein KEAP1, enabling Nrf2 to increase the expression of downstream genes with anti-oxidant and anti-inflammatory capacities. The activation of Nrf2 is required for the anti-inflammatory action of itaconate. We describe the use of a new cell-permeable itaconate derivative, 4-octyl itaconate, which is protective against lipopolysaccharide-induced lethality in vivo and decreases cytokine production. We show that type I interferons boost the expression of Irg1 (also known as Acod1) and itaconate production. Furthermore, we find that itaconate production limits the type I interferon response, indicating a negative feedback loop that involves interferons and itaconate. Our findings demonstrate that itaconate is a crucial anti-inflammatory metabolite that acts via Nrf2 to limit inflammation and modulate type I interferons.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Itaconate displays anti-inflammatory properties, in part because it activates transcription factor Nrf2, which has antioxidant and anti-inflammatory activity.
“Itaconate displays anti-inflammatory properties, in part because of its ability to activate the transcription factor Nrf2, which has antioxidant and anti-inflammatory activity (200).”
From Regulation and function of the mammalian tricarboxylic acid cycle (2023) · cites this paper as [200]
IRG1 is significantly increased in A20-deficient macrophages.
“IRG1 was also found to be significantly increased in A20-deficient macrophages”
From Coupling Krebs cycle metabolites to signalling in immunity and cancer (2018) · cites this paper as [68]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Targeting the KEAP1-NRF2 system to prevent kidney disease progression
Nezu, M., Suzuki, N., & Yamamoto, M. (2017) · American Journal of Nephrology · doi:10.1159/000475890 · Cited by 3,447 · see citing works
Mills, E. L., Kelly, B., Logan, A., Costa, A. S. H., Varma, M., Bryant, C. E., Tourlomousis, P., Däbritz, J. H. M., Gottlieb, E., Latorre, I., et al. (2016) · Cell · doi:10.1016/j.cell.2016.08.064 · Cited by 2,291 · see citing works
Self-citationInterleukin-1 in the pathogenesis and treatment of inflammatory diseases
Dinarello, C. A. (2011) · Blood · doi:10.1182/blood-2010-07-273417 · Cited by 2,248 · see citing works
The Nrf2 regulatory network provides an interface between redox and intermediary metabolism
Hayes, J. D., & Dinkova‐Kostova, A. T. (2014) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2014.02.002 · Cited by 2,158 · see citing works
Self-citationDinkova-Kostova, A. T., Holtzclaw, W. D., Cole, R. N., Itoh, K., Wakabayashi, N., Katoh, Y., Yamamoto, M., & Talalay, P. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.172398899 · Cited by 1,947 · see citing works
Self-citationNrf2 suppresses macrophage inflammatory response by blocking proinflammatory cytokine transcription
Kobayashi, E. H., Suzuki, T., Funayama, R., Nagashima, T., Hayashi, M., Sekine, H., Tanaka, N., Moriguchi, T., Motohashi, H., Nakayama, K., et al. (2016) · Nature Communications · doi:10.1038/ncomms11624 · Cited by 1,878 · see citing works
Akerboom, T. P. M., & Sies, H. (1981) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(81)77050-2 · Cited by 1,580 · see citing works
Lampropoulou, V., Sergushichev, A., Bambousková, M., Nair, S., Vincent, E. E., Loginicheva, E., Cervantes‐Barragán, L., Ma, X., Huang, S. C., Griss, T., et al. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.06.004 · Cited by 1,547 · see citing works
Zhang, D. D., & Hannink, M. (2003) · Molecular and Cellular Biology · doi:10.1128/mcb.23.22.8137-8151.2003 · Cited by 1,480 · see citing works
Immune-responsive gene 1 protein links metabolism to immunity by catalyzing itaconic acid production
Michelucci, A., Cordes, T., Ghelfi, J., Pailot, A., Reiling, N., Goldmann, O., Binz, T., Wegner, A., Tallam, A., Rausell, A., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1218599110 · Cited by 1,191 · see citing works
Linker, R. A., Lee, D.-H., Ryan, S., van Dam, A. M., Conrad, R., Bista, P., Zeng, W., Hronowsky, X., Buko, A., Chollate, S., et al. (2011) · Brain · doi:10.1093/brain/awq386 · Cited by 1,155 · see citing works
Nrf2 is a critical regulator of the innate immune response and survival during experimental sepsis
Thimmulappa, R. K. (2006) · Journal of Clinical Investigation · doi:10.1172/jci25790 · Cited by 1,028 · see citing works
Type I Interferon Inhibits Interleukin-1 Production and Inflammasome Activation
Guarda, G., Braun, M., Staehli, F., Tardivel, A., Mattmann, C., Förster, I., Farlik, M., Decker, T., Pasquier, R. D., Romero, P. J., et al. (2011) · Immunity · doi:10.1016/j.immuni.2011.02.006 · Cited by 924 · see citing works
Lee, J., Calkins, M. J., Chan, K., Kan, Y. W., & Johnson, J. A. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m211558200 · Cited by 783 · see citing works
Cordes, T., Wallace, M., Michelucci, A., Divakaruni, A. S., Sapcariu, S. C., Sousa, C., Koseki, H., Cabrales, P., Murphy, A. N., Hiller, K., et al. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.685792 · Cited by 526 · see citing works
Prochaska, H. J., & Santamaria, A. B. (1988) · Analytical Biochemistry · doi:10.1016/0003-2697(88)90292-8 · Cited by 495 · see citing works
McMahon, M. J., Lamont, D. J., Beattie, K. A., & Hayes, J. D. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1007387107 · Cited by 445 · see citing works
Itaconic acid is a mammalian metabolite induced during macrophage activation
Strelko, C. L., Lu, W., Dufort, F. J., Seyfried, T. N., Chiles, T. C., Rabinowitz, J. D., & Roberts, M. F. (2011) · Journal of the American Chemical Society · doi:10.1021/ja2070889 · Cited by 391 · see citing works
Keap1, the cysteine-based mammalian intracellular sensor for electrophiles and oxidants
Dinkova‐Kostova, A. T., Kostov, R. V., & Canning, P. (2016) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2016.08.005 · Cited by 332 · see citing works
Self-citationFreigang, S., Ampenberger, F., Spohn, G., Heer, S., Shamshiev, A. T., Kisielow, J., Hersberger, M., Yamamoto, M., Bachmann, M. F., & Kopf, M. (2011) · European Journal of Immunology · doi:10.1002/eji.201041316 · Cited by 300 · see citing works
Naujoks, J., Tabeling, C., Dill, B. D., Hoffmann, C., Brown, A. S., Kunze, M., Kempa, S., Peter, A., Mollenkopf, H.-J., Dorhoi, A., et al. (2016) · PLOS Pathogens · doi:10.1371/journal.ppat.1005408 · Cited by 261 · see citing works
Piantadosi, C. A., Withers, C. M., Bartz, R. R., MacGarvey, N. C., Fu, P. P., Sweeney, T. E., Welty‐Wolf, K. E., & Suliman, H. B. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.207738 · Cited by 250 · see citing works
Brennan, M. S., Matos, M. F., Li, B., Hronowski, X., Gao, B., Juhasz, P., Rhodes, K. J., & Scannevin, R. H. (2015) · PLOS ONE · doi:10.1371/journal.pone.0120254 · Cited by 188 · see citing works
The “Prochaska” Microtiter Plate Bioassay for Inducers of NQO1
Fahey, J. W., Dinkova‐Kostova, A. T., Stephenson, K. K., & Talalay, P. (2004) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(04)82014-7 · Cited by 157 · see citing works
Self-citationThe Human Knockout Gene CLYBL Connects Itaconate to Vitamin B12
Shen, H., Campanello, G. C., Flicker, D., Grabarek, Z., Hu, J., Luo, C., Banerjee, R. V., & Mootha, V. K. (2017) · Cell · doi:10.1016/j.cell.2017.09.051 · Cited by 152 · see citing works
Dimethyl Itaconate Is Not Metabolized into Itaconate Intracellularly
ElAzzouny, M., Tom, C. T. M. B., Evans, C. R., Olson, L. L., Tanga, M. J., Gallagher, K. A., Martin, B. R., & Burant, C. F. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.c117.775270 · Cited by 125 · see citing works
Tallam, A., Perumal, T. M., Antony, P. M. A., Jäger, C., Fritz, J. V., Vallar, L., Balling, R., del Sol, A., & Michelucci, A. (2016) · PLoS ONE · doi:10.1371/journal.pone.0149050 · Cited by 103 · see citing works
The mitochondrial dicarboxylate and 2‐oxoglutarate carriers do not transport glutathione
Booty, L. M., King, M. S., Thangaratnarajah, C., et al. (2015) · FEBS Letters · doi:10.1016/j.febslet.2015.01.027 · Cited by 63 · see citing works
Self-citationSubunit NDUFV3 is present in two distinct isoforms in mammalian complex I
Bridges, H. R., Mohammed, K., Harbour, M. E., & Hirst, J. (2017) · Biochimica et Biophysica Acta (BBA) - Bioenergetics · doi:10.1016/j.bbabio.2016.12.001 · Cited by 38 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Mitochondrial TCA cycle metabolites control physiology and disease
Martínez-Reyes, I., & Chandel, N. S. (2020) · Nature Communications · doi:10.1038/s41467-019-13668-3 · Cited by 2,813 · see citing works
Defining trained immunity and its role in health and disease
Netea, M. G., Domínguez-Andrés, J., Barreiro, L. B., Chavakis, T., Divangahi, M., Fuchs, E., Joosten, L. A. B., van der Meer, J. W. M., Mhlanga, M. M., Mulder, W. J. M., et al. (2020) · Nature Reviews Immunology · doi:10.1038/s41577-020-0285-6 · Cited by 2,690 · see citing works
The metabolic signature of macrophage responses
Viola, A., Munari, F., Sánchez-Rodríguez, R., Scolaro, T., & Castegna, A. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01462 · Cited by 2,021 · see citing works
Identification of bioactive metabolites using activity metabolomics
Rinschen, M. M., Ivanisevic, J., Giera, M., & Siuzdak, G. (2019) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-019-0108-4 · Cited by 1,008 · see citing works
Lactate modulation of immune responses in inflammatory versus tumour microenvironments
Certo, M., Tsai, C.-H., Pucino, V., Ho, P.-C., & Mauro, C. (2021) · Nature Reviews Immunology · doi:10.1038/s41577-020-0406-2 · Cited by 924 · see citing works
The role of HIF in immunity and inflammation
McGettrick, A. F., & O’Neill, L. A. J. (2020) · Cell Metabolism · doi:10.1016/j.cmet.2020.08.002 · Cited by 768 · see citing works
Self-citationThe Keap1-Nrf2 System: A Mediator between Oxidative Stress and Aging
Yu, C., & Xiao, J.-H. (2021) · Oxidative Medicine and Cellular Longevity · doi:10.1155/2021/6635460 · Cited by 537 · see citing works
Regulation and function of the mammalian tricarboxylic acid cycle
Arnold, P. K., & Finley, L. W. S. (2023) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2022.102838 · Cited by 535 · see citing works
“Itaconate displays anti-inflammatory properties, in part because of its ability to activate the transcription factor Nrf2, which has antioxidant and anti-inflammatory activity (200).”
BackgroundChronic inflammation and the hallmarks of aging
Baechle, J. J., Chen, N., Makhijani, P., Winer, S., Furman, D., & Winer, D. A. (2023) · Molecular Metabolism · doi:10.1016/j.molmet.2023.101755 · Cited by 471 · see citing works
Krebs cycle Reborn in macrophage immunometabolism
Ryan, D. G., & O'Neill, L. A. J. (2020) · Annual Review of Immunology · doi:10.1146/annurev-immunol-081619-104850 · Cited by 444 · see citing works
Self-citationMetabolic regulatory crosstalk between tumor microenvironment and tumor-associated macrophages
Chen, D., Zhang, X., Li, Z., & Zhu, B. (2021) · Theranostics · doi:10.7150/thno.51777 · Cited by 390 · see citing works
Coupling Krebs cycle metabolites to signalling in immunity and cancer
Ryan, D. G., Murphy, M. P., Frezza, C., Prag, H. A., Chouchani, E. T., O’Neill, L. A., & Mills, E. L. (2018) · Nature Metabolism · doi:10.1038/s42255-018-0014-7 · Cited by 398 · see citing works
Self-citationCircadian clock protein BMAL1 regulates IL-1β in macrophages via NRF2
Early, J. O., Menon, D., Wyse, C. A., Cervantes-Silva, M. P., Zaslona, Z., Carroll, R. G., Palsson-McDermott, E. M., Angiari, S., Ryan, D. G., Corcoran, S. E., et al. (2018) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1800431115 · Cited by 389 · see citing works
Self-citationEpigenetic regulation of the innate immune response to infection
Zhang, Q., & Cao, X. (2019) · Nature Reviews Immunology · doi:10.1038/s41577-019-0151-6 · Cited by 366 · see citing works
Microglia: Agents of the CNS Pro-Inflammatory Response
Rodríguez-Gómez, J. A., Kavanagh, E., Engskog-Vlachos, P., Engskog, M. K. R., Herrera, A. J., Espinosa-Oliva, A. M., Joseph, B., Hajji, N., Venero, J. L., & Burguillos, M. A. (2020) · Cells · doi:10.3390/cells9071717 · Cited by 365 · see citing works
Immunity, Hypoxia, and Metabolism–the Ménage à Trois of Cancer: Implications for Immunotherapy
Riera-Domingo, C., Audigé, A., Granja, S., Cheng, W.-C., Ho, P.-C., Baltazar, F., Stockmann, C., & Mazzone, M. (2020) · Physiological Reviews · doi:10.1152/physrev.00018.2019 · Cited by 310 · see citing works
Macrophage Polarization and Reprogramming in Acute Inflammation: A Redox Perspective
Pérez, S., & Rius-Pérez, S. (2022) · Antioxidants · doi:10.3390/antiox11071394 · Cited by 312 · see citing works
Olagnier, D., Brandtoft, A. M., Gunderstofte, C., Villadsen, N. L., Krapp, C., Thielke, A. L., Laustsen, A., Peri, S., Hansen, A. L., Bonefeld, L., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-05861-7 · Cited by 282 · see citing works
Self-citationCameron, A. M., Castoldi, A., Sanin, D. E., Flachsmann, L. J., Field, C. S., Puleston, D. J., Kyle, R. L., Patterson, A. E., Hässler, F., Buescher, J. M., et al. (2019) · Nature Immunology · doi:10.1038/s41590-019-0336-y · Cited by 269 · see citing works
Thirty years of NRF2: advances and therapeutic challenges.
Zhang, D. D. (2025) · Nature Reviews Drug Discovery · doi:10.1038/s41573-025-01145-0 · Cited by 282 · see citing works
Nitric Oxide in Macrophage Immunometabolism: Hiding in Plain Sight
Palmieri, E. M., McGinity, C., Wink, D. A., & McVicar, D. W. (2020) · Metabolites · doi:10.3390/metabo10110429 · Cited by 237 · see citing works
Lee, S., Devanney, N. A., Golden, L. R., Smith, C. T., Schwartz, J. L., Walsh, A. E., Clarke, H. A., Goulding, D. S., Allenger, E. J., Morillo-Segovia, G., et al. (2023) · Cell Reports · doi:10.1016/j.celrep.2023.112196 · Cited by 203 · see citing works
Yang, C., Zhang, Y., Lin, S., Liu, Y., & Li, W. (2021) · Aging · doi:10.18632/aging.202774 · Cited by 174 · see citing works
Polarization of Rheumatoid Macrophages by TNF Targeting Through an IL-10/STAT3 Mechanism
Degboé, Y., Rauwel, B., Baron, M., Boyer, J.-F., Ruyssen-Witrand, A., Constantin, A., & Davignon, J.-L. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00003 · Cited by 174 · see citing works
The Oncogenic Action of NRF2 Depends on De-glycation by Fructosamine-3-Kinase
Sanghvi, V. R., Leibold, J., Mina, M., Mohan, P., Berishaj, M., Li, Z., Miele, M. M., Lailler, N., Zhao, C., de Stanchina, E., et al. (2019) · Cell · doi:10.1016/j.cell.2019.07.031 · Cited by 155 · see citing works
Molecular mechanisms in liver repair and regeneration: from physiology to therapeutics
Ma, X., Huang, T., Chen, X., Li, Q., Liao, M., Fu, L., Huang, J., Yuan, K., Wang, Z., & Zeng, Y. (2025) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-02104-8 · Cited by 133 · see citing works
Pan, W., Zhao, J., Wu, J., Xu, D., Meng, X., Jiang, P., Shi, H., Ge, X., Yang, X., Hu, M., et al. (2023) · Microbiome · doi:10.1186/s40168-023-01471-8 · Cited by 113 · see citing works
Metabolic reprogramming in tumors: Contributions of the tumor microenvironment
Lane, A. N., Higashi, R. M., & Fan, T. W.-M. (2020) · Genes & Diseases · doi:10.1016/j.gendis.2019.10.007 · Cited by 91 · see citing works
Gut microbiome-mediated metabolism effects on immunity in rural and urban African populations
Stražar, M., Temba, G. S., Vlamakis, H., Kullaya, V. I., Lyamuya, F., Mmbaga, B. T., Joosten, L. A. B., van der Ven, A. J. A. M., Netea, M. G., de Mast, Q., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-25213-2 · Cited by 91 · see citing works
Macrophages recycle phagocytosed bacteria to fuel immunometabolic responses
Lesbats, J., Brillac, A., Reisz, J. A., Mukherjee, P., Lhuissier, C., Fernández-Monreal, M., Dupuy, J.-W., Sequeira, A., Tioli, G., De La Calle Arregui, C., et al. (2025) · Nature · doi:10.1038/s41586-025-08629-4 · Cited by 74 · see citing works
Lin, X.-F., Cui, X.-N., Yang, J., Jiang, Y.-F., Wei, T.-J., Xia, L., Liao, X.-Y., Li, F., Wang, D.-D., Li, J., et al. (2024) · Acta Pharmacologica Sinica · doi:10.1038/s41401-024-01389-3 · Cited by 69 · see citing works
Riedelberger, M., Penninger, P., Tscherner, M., Seifert, M., Jenull, S., Brunnhofer, C., Scheidl, B., Tsymala, I., Bourgeois, C., Petryshyn, A., et al. (2020) · Cell Host & Microbe · doi:10.1016/j.chom.2020.01.023 · Cited by 64 · see citing works
Cell deaths: Involvement in the pathogenesis and intervention therapy of COVID-19
Li, X., Zhang, Z., Wang, Z., Gutiérrez-Castrellón, P., & Shi, H. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01043-6 · Cited by 67 · see citing works
Sun, Y., Huang, J., Chen, Y., Shang, H., Zhang, W., Yu, J., He, L., Xing, C., & Zhuang, C. (2020) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2020.104172 · Cited by 73 · see citing works
Induction of a colitogenic phenotype in Th1-like cells depends on interleukin-23 receptor signaling
Pawlak, M., DeTomaso, D., Schnell, A., Meyer zu Horste, G., Lee, Y., Nyman, J., Dionne, D., Regan, B. M. L., Singh, V., Delorey, T., et al. (2022) · Immunity · doi:10.1016/j.immuni.2022.08.007 · Cited by 49 · see citing works
Reprogramming of mitochondrial metabolism by innate immunity
Garaude, J. (2019) · Current Opinion in Immunology · doi:10.1016/j.coi.2018.09.010 · Cited by 33 · see citing works
Dimethyl fumarate: targeting glycolysis to treat MS
Angiari, S., & O’Neill, L. A. (2018) · Cell Research · doi:10.1038/s41422-018-0045-3 · Cited by 27 · see citing works
Self-citationCuadrado, A., Cazalla, E., Bach, A., Bathish, B., Naidu, S. D., DeNicola, G. M., Dinkova-Kostova, A. T., Fernández-Ginés, R., Grochot-Przeczek, A., Hayes, J. D., et al. (2025) · Redox Biology · doi:10.1016/j.redox.2025.103569 · Cited by 28 · see citing works
Self-citationZeng, L., Wang, Y., Huang, Y., Yang, W., Zhou, P., Wan, Y., Tao, K., & Li, R. (2025) · Cell Communication and Signaling · doi:10.1186/s12964-025-02075-5 · Cited by 22 · see citing works
Xu, K., Huang, Q., Lyu, Y., Wang, S., Lu, Y., & Qian, G. (2024) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2024.117200 · Cited by 11 · see citing works
- Authors
- Mills, E. L., Ryan, D. G., Prag, H. A., Dikovskaya, D., Menon, D., Zaslona, Z., Jedrychowski, M. P., Costa, A. S. H., Higgins, M., Hams, E., Szpyt, J., Runtsch, M. C., King, M. S., McGouran, J. F., Fischer, R., Kessler, B. M., McGettrick, A. F., Hughes, M. M., Carroll, R. G., Booty, L. M., Knatko, E. V., Meakin, P. J., Ashford, M. L. J., Modis, L. K., Brunori, G., Sévin, D. C., Fallon, P. G., Caldwell, S. T., Kunji, E. R. S., Chouchani, E. T., Frezza, C., Dinkova-Kostova, A. T., Hartley, R. C., Murphy, M. P., & O’Neill, L. A.
- Affiliations
- Harvard University (US)
- Trinity College Dublin (IE)
- University of Cambridge (GB)
- University of Dundee (GB)
- University of Oxford (GB)
- GlaxoSmithKline (United Kingdom) (GB)
- GlaxoSmithKline (Germany) (DE)
- University of Glasgow (GB)
- ORCID
- Mills, Evanna L.
- Ryan, Dylan G.
- Prag, Hiran A.
- Dikovskaya, Dina
- Costa, Ana S. H.
- Higgins, Maureen
- Hams, Emily
- Runtsch, Marah C.
- King, Martin S.
- McGouran, Joanna F.
- Kessler, Benedikt M.
- McGettrick, Anne F.
- Hughes, Mark M.
- Carroll, Richard G.
- Booty, Lee M.
- Meakin, Paul J.
- Ashford, Michael L. J.
- Modis, Louise K.
- Sévin, Daniel C.
- Fallon, Padraic G.
- Caldwell, Stuart T.
- Kunji, Edmund R. S.
- Chouchani, Edward T.
- Frezza, Christian
- Hartley, Richard C.
- Murphy, Michael P.
- Venue
- Nature
- Published
- 2018-03-28
- Volume
- 556
- Issue
- 7699
- Pages
- 113-117
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC6047741
- OpenAlex
- W2794844698
- Cited by
- 1,885
- References
- 29
- Citations by year
- 2026: 285 · 2025: 273 · 2024: 296 · 2023: 224 · 2022: 236 · 2021: 197 · 2020: 191 · 2019: 123 · 2018: 58
- FWCI
- 50.70
- Type
- journal article
- Language
- en
- Open access
- green
- eprints.gla.ac.uk
- Licence
- cc-by-sa
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (acceptedVersion, cc-by-sa)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Discovery Research Portal (University of Dundee) (submittedVersion, other-oa)
- White Rose Research Online (University of Leeds, The University of Sheffield, University of York) (submittedVersion)
- Research Explorer (The University of Manchester) (submittedVersion)
- Apollo (University of Cambridge) (submittedVersion)
- Apollo
- Funders
- GlaxoSmithKline
- University of Dundee
- Wellcome Trust (110158/Z/15/Z, 205455, 110159/Z/ 15/Z, /Z/15/Z, 109443/Z/15/Z)
- Cancer Research UK (C20953 / A18644, A18644, C20953, 18644)
- British Heart Foundation (FS/18/38/33659, PG/15/44/31574)
- Science Foundation Ireland (SFI 12/IA/1531, 12/IA/1531)
- Medical Research Council (MC_U105663139, C20953/A18644, MC_UU_00015/3, MC-U105663142, MC_UU_00015/7, MC_UU_12022/6)
- Biotechnology and Biological Sciences Research Council (BB/L01923X/1, BB/R50564X/1)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics, phytochemicals, and oxidative stress
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › NF-κB Signaling Pathways
- Keywords
- Nrf2, Keap1, cysteine alkylation, macrophages, lipopolysaccharide, 4-octyl itaconate, type I interferon, IRG1, ACOD1, oxidative stress, inflammation, cysteine sulfoxides, endogenous metabolites, inflammatory cytokines
- MeSH terms
- Kelch-Like ECH-Associated Protein 1, Alkylation, Animals, Anti-Inflammatory Agents, Carboxy-Lyases, Cattle, Cysteine, Female, Humans, Hydro-Lyases, Lipopolysaccharides, Macrophages, Proteins, Succinates, Cytokines, Interferon-beta, Rats, Wistar, Feedback, Physiological, NF-E2-Related Factor 2, Mice, Rats, HEK293 Cells
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
