The DOI matches its Crossref record; 46 of the 46 references it cites were found in a registry or an index.
Transcription Factor Nrf2 Regulates Inflammation by Mediating the Effect of 15-Deoxy-Δ12,14-Prostaglandin J2
Open accessAbstract
Activated macrophages express high levels of Nrf2, a transcription factor that positively regulates the gene expression of antioxidant and detoxication enzymes. In this study, we examined how Nrf2 contributes to the anti-inflammatory process. As a model system of acute inflammation, we administered carrageenan to induce pleurisy and found that in Nrf2-deficient mice, tissue invasion by neutrophils persisted during inflammation and the recruitment of macrophages was delayed. Using an antibody against 15-deoxy-Delta(12,14)-prostaglandin J(2) (15d-PGJ(2)), it was observed that macrophages from pleural lavage accumulate 15d-PGJ(2). We show that in mouse peritoneal macrophages 15d-PGJ(2) can activate Nrf2 by forming adducts with Keap1, resulting in an Nrf2-dependent induction of heme oxygenase 1 and peroxiredoxin I (PrxI) gene expression. Administration of the cyclooxygenase 2 inhibitor NS-398 to mice with carrageenan-induced pleurisy caused persistence of neutrophil recruitment and, in macrophages, attenuated the 15d-PGJ(2) accumulation and PrxI expression. Administration of 15d-PGJ(2) into the pleural space of NS-398-treated wild-type mice largely counteracted both the decrease in PrxI and persistence of neutrophil recruitment. In contrast, these changes did not occur in the Nrf2-deficient mice. These results demonstrate that Nrf2 regulates the inflammation process downstream of 15d-PGJ(2) by orchestrating the recruitment of inflammatory cells and regulating the gene expression within those cells.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
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?
In the citing paper
“Nrf2 plays a role in regulating the anti-inflammatory response through redox control and activation of ARE-mediated anti-inflammatory genes, including the expression of the antioxidant genes NQO1, HO-1, and PRX1, all of which exhibit anti-inflammatory effects [191,192,193,194].”
From Nrf2 and Oxidative Stress: A General Overview of Mechanisms and Implications in Human Disease (2022) · cites this paper as [194]
Citations
Cites
Inhibition of Prostaglandin Synthesis as a Mechanism of Action for Aspirin-like Drugs
VANE, J. R. (1971) · Nature New Biology · doi:10.1038/newbio231232a0 · Cited by 8,605
Itoh, K., Chiba, T., Takahashi, S., Ishii, T., Igarashi, K., Katoh, Y., Oyake, T., Hayashi, N., Satoh, K., Hatayama, I., et al. (1997) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.1997.6943 · Cited by 3,999
Itoh, K., Wakabayashi, N., Katoh, Y., Ishii, T., Igarashi, K., Engel, J. D., & Yamamoto, M. (1999) · Genes & Development · doi:10.1101/gad.13.1.76 · Cited by 3,634
Self-citationThe peroxisome proliferator-activated receptor-γ is a negative regulator of macrophage activation
Ricote, M., Li, A. C., Willson, T. M., Kelly, C. J., & Glass, C. K. (1998) · Nature · doi:10.1038/34178 · Cited by 3,525
PPAR-γ agonists inhibit production of monocyte inflammatory cytokines
Jiang, C., Ting, A. T., & Seed, B. (1998) · Nature · doi:10.1038/34184 · Cited by 2,899
Points of control in inflammation
Nathan, C. (2002) · Nature · doi:10.1038/nature01320 · Cited by 2,738
Carbon monoxide has anti-inflammatory effects involving the mitogen-activated protein kinase pathway
Otterbein, L. E., Bach, F. H., Alam, J., Soares, M., Tao Lu, H., Wysk, M., Davis, R. J., Flavell, R. A., & Choi, A. M. K. (2000) · Nature Medicine · doi:10.1038/74680 · Cited by 2,153
Dinkova-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
Self-citationSeibert, K., Zhang, Y., Leahy, K., Hauser, S. D., Masferrer, J. L., Perkins, W., Lee, L., & Isakson, P. C. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.25.12013 · Cited by 1,551
Warner, T. D., Giuliano, F., Vojnovic, I., Bukasa, A., Mitchell, J. A., & Vane, J. R. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.13.7563 · Cited by 1,521
Flagged first, then by citations
Research works printed but not linked: 1
- Narumiya S., 1987, J. Pharmacol. Exp. Ther., 242, 306
Cited by
Sorted by citations
Hayes, J. D., Flanagan, J. U., & Jowsey, I. R. (2004) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.45.120403.095857 · Cited by 3,565
Cell Survival Responses to Environmental Stresses Via the Keap1-Nrf2-ARE Pathway
Kensler, T. W., Wakabayashi, N., & Biswal, S. (2007) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.46.120604.141046 · Cited by 3,630
The KEAP1-NRF2 system: a thiol-based sensor-effector apparatus for maintaining redox homeostasis
Yamamoto, M., Kensler, T. W., & Motohashi, H. (2018) · Physiological Reviews · doi:10.1152/physrev.00023.2017 · Cited by 1,968
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
Self-citationNrf2 signaling pathway: pivotal roles in inflammation
Ahmed, S. M. U., Luo, L., Namani, A., Wang, X. J., & Tang, X. (2017) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2016.11.005 · Cited by 1,794
Nrf2–Keap1 defines a physiologically important stress response mechanism
Motohashi, H., & Yamamoto, M. (2004) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2004.09.003 · Cited by 1,725
Self-citationNRF2 and the Hallmarks of Cancer
Rojo de la Vega, M., Chapman, E., & Zhang, D. D. (2018) · Cancer Cell · doi:10.1016/j.ccell.2018.03.022 · Cited by 1,672
“Consistently, many studies have shown that Nrf2−/− mice have persistent inflammation (Itoh et al., 2004, Johnson et al., 2010, Kong et al., 2010).”
BackgroundAn Overview of Nrf2 Signaling Pathway and Its Role in Inflammation
Saha, S., Buttari, B., Panieri, E., Profumo, E., & Saso, L. (2020) · Molecules · doi:10.3390/molecules25225474 · Cited by 1,460
“Here, it was postulated that the presence of highly reactiveα,β-unsaturated carbonyl group might confer to cyPGs the ability to form Michael adducts with nucleophilic molecules and to induce covalent modifications of target proteins, a mechanism that might be responsible for the activation of Nrf2 [192].”
BackgroundNrf2 and Oxidative Stress: A General Overview of Mechanisms and Implications in Human Disease
Ngo, V., & Duennwald, M. L. (2022) · Antioxidants · doi:10.3390/antiox11122345 · Cited by 1,130
Molecular Mechanisms Activating the Nrf2-Keap1 Pathway of Antioxidant Gene Regulation
Kobayashi, M., & Yamamoto, M. P. (2005) · Antioxidants and Redox Signaling · doi:10.1089/ars.2005.7.385 · Cited by 1,087
Self-citationInflammation, a Key Event in Cancer Development
Lu, H., Ouyang, W., & Huang, C. (2006) · Molecular Cancer Research · doi:10.1158/1541-7786.mcr-05-0261 · Cited by 1,049
“The regulatory role of Nrf2 in the resolution of inflammation was through the induction by a prostaglandin product of COX-2 (207).”
BackgroundOxidative stress in health and disease: The therapeutic potential of Nrf2 activation
Hybertson, B. M., Gao, B., Bose, S. K., & McCord, J. M. (2011) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2011.10.006 · Cited by 1,046
“…(Wild et al., 1999), Phase II detoxification or ‘‘stress-response’’ genes (Itoh et al., 1999a), genes involved in limiting the inflammatory process (Itoh et al., 2004), genes involved in limiting pulmonary fibrosis (Kikuchi et al., 2010), and genes conferring protection against…”
BackgroundKobayashi, A., Kang, M.-I., Watai, Y., Tong, K. I., Shibata, T., Uchida, K., & Yamamoto, M. P. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.26.1.221-229.2006 · Cited by 947
“To address this possibility, we utilized biotinylated 15d-PGJ2 (17, 36).”
BackgroundMethodSelf-citationBardoxolone Methyl and Kidney Function in CKD with Type 2 Diabetes
Pergola, P. E., Raskin, P., Toto, R. D., Meyer, C. J., Huff, J. W., Grossman, E. B., Krauth, M., Ruiz, S., Audhya, P., Christ-Schmidt, H., et al. (2011) · New England Journal of Medicine · doi:10.1056/nejmoa1105351 · Cited by 890
Kobayashi, M., & Yamamoto, M. P. (2006) · Advances in Enzyme Regulation · doi:10.1016/j.advenzreg.2006.01.007 · Cited by 862
Self-citationTebay, L. E., Robertson, H., Durant, S. T., Vitale, S. R., Penning, T. M., Dinkova-Kostova, A. T., & Hayes, J. D. (2015) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2015.06.021 · Cited by 837
“During carrageenaninduced acute inflammation, it has been proposed that accumulation of 15-deoxy-Δ12,14prostaglandin J2 in peritoneal macrophages is responsible for activation of Nrf2 through inhibition of Keap1 [194].”
Kobayashi, M., Li, L., Iwamoto, N., Nakajima‐Takagi, Y., Kaneko, H., Nakayama, Y., Eguchi, M., Wada, Y., Kumagai, Y., & Yamamoto, M. P. (2008) · Molecular and Cellular Biology · doi:10.1128/mcb.01080-08 · Cited by 641
“The carrageenan-induced pleurisy model of acute lung injury was used to demonstrate the relationship between Nrf2 activation and anti-inflammation and that accumulation of 15d-PGJ2 mediates this relation ( 11 ).”
BackgroundSelf-citationWhen NRF2 Talks, Who's Listening?
Wakabayashi, N., Slocum, S. L., Skoko, J. J., Shin, S., & Kensler, T. W. (2010) · Antioxidants & Redox Signaling · doi:10.1089/ars.2010.3216 · Cited by 595
Basic Principles and Emerging Concepts in the Redox Control of Transcription Factors
Brigelius‐Flohé, R., & Flohé, L. (2011) · Antioxidants and Redox Signaling · doi:10.1089/ars.2010.3534 · Cited by 590
Dinkova‐Kostova, A. T., Liby, K. T., Stephenson, K. K., Holtzclaw, W. D., Gao, X., Suh, N., Williams, C. R., Risingsong, R., Honda, T., Gribble, G. W., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0500815102 · Cited by 575
Coordination of ER and oxidative stress signaling: The PERK/Nrf2 signaling pathway
Cullinan, S. B., & Diehl, J. A. (2006) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2005.09.018 · Cited by 554
Nrf2 signaling: An adaptive response pathway for protection against environmental toxic insults
Osburn, W. O., & Kensler, T. W. (2007) · Mutation Research/Reviews in Mutation Research · doi:10.1016/j.mrrev.2007.11.006 · Cited by 549
Discovery of the Negative Regulator of Nrf2, Keap1: A Historical Overview
Itoh, K., Mimura, J., & Yamamoto, M. P. (2010) · Antioxidants and Redox Signaling · doi:10.1089/ars.2010.3222 · Cited by 521
Self-citationNa, H., & Surh, Y. (2007) · Food and Chemical Toxicology · doi:10.1016/j.fct.2007.10.006 · Cited by 486
Eggler, A. L., Liu, G., Pezzuto, J. M., van Breemen, R. B., & Mesecar, A. D. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0502402102 · Cited by 476
Yang, C., Zhang, X., Fan, H., & Liu, Y. (2009) · Brain Research · doi:10.1016/j.brainres.2009.05.009 · Cited by 444
“…upon stimulation by electrophilic agents or compounds that possess the ability to modify thiol groups (Li et al., 2004; Kobayashi et al., 2004), Keap 1 repression of Nrf2 is lost, allowing Nrf2 protein to translocate into the nucleus where it activates ARE on the HO-1 promoter (Itoh et al., 2004).”
Mo, C., Wang, L., Zhang, J., Numazawa, S., Tang, H. W., Tang, X., Han, X., Li, J., Yang, M., Wang, Z., et al. (2013) · Antioxidants and Redox Signaling · doi:10.1089/ars.2012.5116 · Cited by 448
“reported COX-2-mediated intracellular accumulation of 15d-PGJ2, which induced Nrf2 activation and consequently in turn regulates the expression antioxidative stress enzymes in inflammatory macrophages (18).”
BackgroundShih, A. Y., Li, P., & Murphy, T. H. (2005) · The Journal of Neuroscience · doi:10.1523/jneurosci.4014-05.2005 · Cited by 413
Suzuki, T., & Yamamoto, M. P. (2017) · Journal of Biological Chemistry · doi:10.1074/jbc.r117.800169 · Cited by 412
Self-citationActivation of NRF2 by Nitrosative Agents and H2O2 Involves KEAP1 Disulfide Formation
Fourquet, S., Guérois, R., Biard, D. S. F., & Tolédano, M. B. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.051714 · Cited by 389
The Role of Keap1 in Cellular Protective Responses
Dinkova‐Kostova, A. T., Holtzclaw, W. D., & Kensler, T. W. (2005) · Chemical Research in Toxicology · doi:10.1021/tx050217c · Cited by 378
Motohashi, H., Katsuoka, F., Engel, J. D., & Yamamoto, M. P. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0305902101 · Cited by 372
Self-citationEnvironmental pollutants and the immune response
Suzuki, T., Hidaka, T., Kumagai, Y., & Yamamoto, M. P. (2020) · Nature Immunology · doi:10.1038/s41590-020-0802-6 · Cited by 376
Self-citationActivation of the Keap1/Nrf2 pathway for neuroprotection by electrophillic phase II inducers
Satoh, T., Okamoto, S.-I., Cui, J., Watanabe, Y., Furuta, K., Suzuki, M., Tohyama, K., & Lipton, S. A. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0505723102 · Cited by 344
Nrf2‐deficient mice are highly susceptible to cigarette smoke‐induced emphysema
Iizuka, T., Ishii, Y., Itoh, K., Kiwamoto, T., Kimura, T., Matsuno, Y., Morishima, Y., Hegab, A. E., Homma, S., Nomura, A., et al. (2005) · Genes to Cells · doi:10.1111/j.1365-2443.2005.00905.x · Cited by 341
“Indeed, Nrf2 plays essential roles in protection against pulmonary inflammation caused by environmental toxins such as butylated hydroxytoluene (Chan & Kan 1999) and hyperoxia (Cho et al. 2002) and regulates inflammation in carrageenan-induced pleurisy (Itoh et al. 2004).”
BackgroundSelf-citationThe Nrf2–Keap1 defence pathway: Role in protection against drug-induced toxicity
Copple, I. M., Goldring, C. E., Kitteringham, N. R., & Park, B. K. (2007) · Toxicology · doi:10.1016/j.tox.2007.10.029 · Cited by 336
Plasma Medicine: A Field of Applied Redox Biology
von Woedtke, T., Schmidt, A., Bekeschus, S., Wende, K., & Weltmann, K. (2019) · In Vivo · doi:10.21873/invivo.11570 · Cited by 335
Free Radicals, Mitochondria, and Oxidized Lipids
Gutiérrez, J., Ballinger, S. W., Darley-Usmar, V. M., & Landar, A. L. (2006) · Circulation Research · doi:10.1161/01.res.0000248212.86638.e9 · Cited by 320
Molecular Basis of Electrophilic and Oxidative Defense: Promises and Perils of Nrf2
Ma, Q., & He, X. (2012) · Pharmacological Reviews · doi:10.1124/pr.110.004333 · Cited by 317
“The cyclopentenone prostaglandins 15-deoxy(12,14)-prostaglandin J2 and prostaglandin A2 activate Nrf2 to induce heme oxygenase 1 (HO-1) and peroxiredoxin 1, which contribute to the anti-inflammatory activity of Nrf2 (Itoh et al., 2004).”
Chemoprevention through the Keap1–Nrf2 signaling pathway by phase 2 enzyme inducers
Kwak, M.-K., Wakabayashi, N., & Kensler, T. W. (2004) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/j.mrfmmm.2004.06.041 · Cited by 312
Formation and signaling actions of electrophilic lipids
Schopfer, F. J., Cipollina, C., & Freeman, B. A. (2011) · Chemical Reviews · doi:10.1021/cr200131e · Cited by 299
Suzuki, M., Betsuyaku, T., Ito, Y., Nagai, K., Nasuhara, Y., Kaga, K., Kondo, S., & Nishimura, M. (2008) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/rcmb.2007-0424oc · Cited by 286
Chen, C., & Kong, A. T. (2005) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2005.04.004 · Cited by 269
Heme Oxygenase-1 and the Vascular Bed: From Molecular Mechanisms to Therapeutic Opportunities
Łoboda, A., Jaźwa, A., Grochot‐Przeczek, A., Rutkowski, A. J., Cisowski, J., Agarwal, A., Józkowicz, A., & Dulak, J. (2008) · Antioxidants and Redox Signaling · doi:10.1089/ars.2008.2043 · Cited by 265
TrxR1 as a Potent Regulator of the Nrf2-Keap1 Response System
Cebula, M., Schmidt, E. E., & Arnér, E. S. J. (2015) · Antioxidants and Redox Signaling · doi:10.1089/ars.2015.6378 · Cited by 251
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
“39,112).”
Ishii, Y., Itoh, K., Morishima, Y., Kimura, T., Kiwamoto, T., IIzuka, T., Hegab, A. E., Hosoya, T., Nomura, A., Sakamoto, T., et al. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.175.10.6968 · Cited by 248
“Moreover, it is reported that Nrf2 regulates inflammation in carrageenan-induced pleurisy and acute lung injury (21, 22).”
BackgroundSelf-citationTricarboxylic Acid (TCA) Cycle Intermediates: Regulators of Immune Responses
Choi, I., Son, H., & Baek, J.-H. (2021) · Life · doi:10.3390/life11010069 · Cited by 257
Protein Damage by Reactive Electrophiles: Targets and Consequences
Liebler, D. C. (2007) · Chemical Research in Toxicology · doi:10.1021/tx700235t · Cited by 235
The Flavanol (−)-Epicatechin Prevents Stroke Damage through the Nrf2/HO1 Pathway
Shah, Z. A., Li, R.-C., Ahmad, A. S., Kensler, T. W., Yamamoto, M. P., Biswal, S. S., & Doré, S. (2010) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2010.53 · Cited by 236
“& 2010 ISCBFM All rights reserved 0271-678X/10 $32.00 www.jcbfm.com (Gong et al, 2002; Itoh et al, 2004).”
BackgroundInfluentialSelf-citationLevonen, A., Hill, B. G., Kansanen, E., Zhang, J., & Darley-Usmar, V. M. (2014) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2014.03.025 · Cited by 235
Transcription factor Nrf2 regulates SHP and lipogenic gene expression in hepatic lipid metabolism
Huang, J., Tabbi‐Anneni, I., Gunda, V., & Wang, L. (2010) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00322.2010 · Cited by 228
Hosoya, T., Maruyama, A., Kang, M.-I., Kawatani, Y., Shibata, T., Uchida, K., Itoh, K., & Yamamoto, M. P. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m502551200 · Cited by 225
Self-citationHarada, N., Kanayama, M., Maruyama, A., Yoshida, A., Tazumi, K., Hosoya, T., Mimura, J., Toki, T., Maher, J. M., Yamamoto, M. P., et al. (2011) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2011.02.001 · Cited by 236
Self-citationSmall molecule modulators of antioxidant response pathway
Hur, W., & Gray, N. S. (2010) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2010.12.009 · Cited by 214
Maines, M. D., & Gibbs, P. (2005) · Biochemical and Biophysical Research Communications - BBRC · doi:10.1016/j.bbrc.2005.08.121 · Cited by 233
Johnson, D. A., Amirahmadi, S., Ward, C., Fabry, Z., & Johnson, J. A. (2009) · Toxicological Sciences · doi:10.1093/toxsci/kfp274 · Cited by 210
“Moreover, exogenous administration of 15d-PGJ2 reversed ALI in WT but not in Nrf2-KO mice, supporting the notion that Nrf2 does indeed modulate inflammatory response (Itoh et al., 2004).”
BackgroundInfluentialTransduction of Redox Signaling by Electrophile-Protein Reactions
Rudolph, T. K., & Freeman, B. Α. (2009) · Science Signaling · doi:10.1126/scisignal.290re7 · Cited by 203
Cardozo, L., Pedruzzi, L. M., Stenvinkel, P., Stockler‐Pinto, M. B., Daleprane, J. B., Leite, M., & Mafra, D. (2013) · Biochimie · doi:10.1016/j.biochi.2013.04.012 · Cited by 202
Nrf2 as a target for cancer chemoprevention
Yu, X. Y., & Kensler, T. W. (2005) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/j.mrfmmm.2005.04.017 · Cited by 199
Nrf2: Molecular and epigenetic regulation during aging
Silva‐Palacios, A., Ostolga-Chavarría, M., Zazueta, C., & Königsberg, M. (2018) · Ageing Research Reviews · doi:10.1016/j.arr.2018.06.003 · Cited by 199
Osburn, W. O., Karim, B. O., Dolan, P. M., Liu, G., Yamamoto, M. P., Huso, D. L., & Kensler, T. W. (2007) · International Journal of Cancer · doi:10.1002/ijc.22943 · Cited by 197
Self-citationChapple, S., Cheng, X.-H., & Mann, G. (2013) · Redox Biology · doi:10.1016/j.redox.2013.04.001 · Cited by 183
Crosstalk of toll-like receptors signaling and Nrf2 pathway for regulation of inflammation
Mohan, S. V., & Gupta, D. (2018) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2018.10.019 · Cited by 221
Lipoxins: nature's way to resolve inflammation
Sharma-Walia, N., & Chandrasekharan, J. A. (2015) · Journal of Inflammation Research · doi:10.2147/jir.s90380 · Cited by 243
Multiple regulations of Keap1/Nrf2 system by dietary phytochemicals
Qin, S., & Hou, D. (2016) · Molecular Nutrition & Food Research · doi:10.1002/mnfr.201501017 · Cited by 191
The Redox Activity of Hemoglobins: From Physiologic Functions to Pathologic Mechanisms
Reeder, B. J. (2010) · Antioxidants & Redox Signaling · doi:10.1089/ars.2009.2974 · Cited by 189
Levonen, A., Inkala, M., Heikura, T., Jauhiainen, S., Jyrkkänen, H.-K., Kansanen, E., Määttä, K. M., Romppanen, E., Turunen, P., Rutanen, J., et al. (2007) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000258868.80079.4d · Cited by 188
Celastrol suppresses colorectal cancer via covalent targeting peroxiredoxin 1
Xu, H., Zhao, H., Ding, C., Jiang, D., Zhao, Z., Li, Y., Ding, X., Gao, J., Zhou, H., Luo, C., et al. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01231-4 · Cited by 194
The Keap1–Nrf2 system as an in vivo sensor for electrophiles
Uruno, A., & Motohashi, H. (2011) · Nitric Oxide · doi:10.1016/j.niox.2011.02.007 · Cited by 187
Roles of Nrf2 in Protecting the Kidney from Oxidative Damage
Nezu, M., & Suzuki, N. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21082951 · Cited by 183
Eggler, A. L., Small, E., Hannink, M., & Mesecar, A. D. (2009) · Biochemical Journal · doi:10.1042/bj20090471 · Cited by 178
Higgins, L. G., Kelleher, M., Eggleston, I. M., Itoh, K., Yamamoto, M. P., & Hayes, J. D. (2009) · Toxicology and Applied Pharmacology · doi:10.1016/j.taap.2009.03.005 · Cited by 178
Self-citationKundu, J. K., & Surh, Y. (2010) · Pharmaceutical Research · doi:10.1007/s11095-010-0096-8 · Cited by 171
The Keap1–Nrf2 Cell Defense Pathway – A Promising Therapeutic Target?
Copple, I. M. (2012) · Advances in pharmacology · doi:10.1016/b978-0-12-398339-8.00002-1 · Cited by 174
Targeting the Nrf2 pathway against cardiovascular disease
Li, J., Ichikawa, T., Janicki, J. S., & Cui, T. (2009) · Expert Opinion on Therapeutic Targets · doi:10.1517/14728220903025762 · Cited by 168
Redox Regulation of Human Thioredoxin Network
Kondo, N., Nakamura, H., Masutani, H., & Yodoi, J. (2006) · Antioxidants and Redox Signaling · doi:10.1089/ars.2006.8.1881 · Cited by 171
CXCL1 and CXCL2 Regulate NLRP3 Inflammasome Activation via G-Protein–Coupled Receptor CXCR2
Boro, M., & Balaji, K. N. (2017) · The Journal of Immunology · doi:10.4049/jimmunol.1700129 · Cited by 167
Nrf2 Suppresses Oxidative Stress and Inflammation in App Knock-In Alzheimer’s Disease Model Mice
Uruno, A., Matsumaru, D., Ryoke, R., Saito, R., Kadoguchi, S., Saigusa, D., Saito, T., Saido, T. C., Kawashima, R., & Yamamoto, M. P. (2020) · Molecular and Cellular Biology · doi:10.1128/mcb.00467-19 · Cited by 168
“ELISA showed that the soluble A (1-40) (F) and A (1-42) levels were comparable among cerebral cortices and hippocampi in AppNLGF and AppNLGF::Keap1FA/FA mouse”
BackgroundMethodSelf-citationNrf2-dependent and -independent Responses to Nitro-fatty Acids in Human Endothelial Cells
Kansanen, E., Jyrkkänen, H.-K., Volger, O. L., Leinonen, H., Kivelä, A. M., Häkkinen, S.-K., Woodcock, S. R., Schopfer, F. J., Horrevoets, A. J., Ylä-Herttuala, S., et al. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.064873 · Cited by 165
Osburn, W. O., Yates, M. S., Dolan, P. D., Chen, S., Liby, K. T., Sporn, M. B., Taguchi, K., Yamamoto, M. P., & Kensler, T. W. (2008) · Toxicological Sciences · doi:10.1093/toxsci/kfn079 · Cited by 158
“Indeed, the lack of an active Nrf2 signaling pathway in mice has been shown to result in increased inflammation and inflammation-mediated oxidative damage in a number of lung and colon disease models (Itoh et al., 2004; Khor et al., 2006; Osburn et al., 2007; Rangasamy et al., 2005; Thimmulappa et al., 2006).”
BackgroundSelf-citationCold atmospheric plasma delivery for biomedical applications
Chen, Z., Chen, G., Obenchain, R. A., Zhang, R., Bai, F., Fang, T., Wang, H., Lu, Y., Wirz, R. E., & Gu, Z. (2022) · Materials Today · doi:10.1016/j.mattod.2022.03.001 · Cited by 162
Blank, V. (2007) · Journal of Molecular Biology · doi:10.1016/j.jmb.2007.11.074 · Cited by 154
Redox regulation of neuronal survival mediated by electrophilic compounds
Satoh, T., & Lipton, S. A. (2006) · Trends in Neurosciences · doi:10.1016/j.tins.2006.11.004 · Cited by 156
Regulation of Nrf2-dependent gene expression by 15-deoxy-Δ12,14-prostaglandin J2
Kansanen, E., Kivelä, A. M., & Levonen, A. (2009) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2009.06.030 · Cited by 151
Żmijewski, J. W., Moellering, D. R., Goffe, C. L., Landar, A. L., Ramachandran, A., & Darley-Usmar, V. M. (2005) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00015.2005 · Cited by 149
“Furthermore, it has been shown that both complex mixtures of oxidized lipids and specific individual molecules, particularly reactive electrophiles, are capable of inducing cell signaling events (18, 20, 26, 27, 33, 37).”
BackgroundLee, Y., Shin, D., Kim, J., Hong, S., Choi, D., Kim, Y.-J., Kwak, M., & Jung, Y. (2010) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2010.06.016 · Cited by 147
Non-thermal Plasma Activates Human Keratinocytes by Stimulation of Antioxidant and Phase II Pathways
Schmidt, A., Dietrich, S., Steuer, A., Weltmann, K., von Woedtke, T., Masur, K., & Wende, K. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.603555 · Cited by 148
Kim, E. H., & Surh, Y. (2006) · Biochemical Pharmacology · doi:10.1016/j.bcp.2006.07.030 · Cited by 149
Villacorta, L., Zhang, J., Garcia-Barrio, M. T., Chen, X.-L., Freeman, B. A., Chen, Y. E., & Cui, T. (2007) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00261.2007 · Cited by 144
Landar, A. L., Żmijewski, J. W., Dickinson, D. A., Goffe, C. L., Johnson, M. S., Milne, G. L., Zanoni, G., Vidari, G., Morrow, J. D., & Darley-Usmar, V. M. (2005) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.01087.2005 · Cited by 139
“This has been demonstrated most clearly with specific lipid oxidation products, particularly those containing an electrophilic carbon center (13, 14, 17, 18, 23, 31).”
Background15-Deoxy-Δ12,14-prostaglandin J2: An Electrophilic Trigger of Cellular Responses
Uchida, K., & Shibata, T. (2007) · Chemical Research in Toxicology · doi:10.1021/tx700177j · Cited by 140
Self-citationIdentification of polymorphisms in the promoter region of the human NRF2 gene
Yamamoto, T., Yoh, K., Kobayashi, A., Ishii, Y., Kure, S., Kôyama, A., Sakamoto, T., Sekizawa, K., Motohashi, H., & Yamamoto, M. P. (2004) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2004.06.112 · Cited by 140
Self-citationRegulation of innate immunity by NADPH oxidase
Segal, B. H., Grimm, M. J., Khan, A. N. H., Han, W., & Blackwell, T. S. (2012) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2012.04.022 · Cited by 140
Oxidative Modification of Proteins: An Emerging Mechanism of Cell Signaling
Wall, S. B., Oh, J., Diers, A. R., & Landar, A. L. (2012) · Frontiers in Physiology · doi:10.3389/fphys.2012.00369 · Cited by 142
“One well characterized protein modified by electrophilic lipids is the Kelch-like ECH-associated protein 1 (Keap1; Itoh et al., 2004; Levonen et al., 2004), which is involved in the redox regulation of transcription (Brigelius-Flohe and Flohe, 2011).”
BackgroundSiow, R. C. M., Li, F. Y. L., Rowlands, D. J., de Winter, P., & Mann, G. E. (2007) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2007.01.004 · Cited by 135
Absolute Amounts and Status of the Nrf2-Keap1-Cul3 Complex within Cells
Iso, T., Suzuki, T., Baird, L., & Yamamoto, M. P. (2016) · Molecular and Cellular Biology · doi:10.1128/mcb.00389-16 · Cited by 130
Self-citationSurh, Y., Na, H., Park, J., Lee, H., Kim, W., Yoon, I., & Kim, D. (2011) · Biochemical Pharmacology · doi:10.1016/j.bcp.2011.07.100 · Cited by 133
“HO-1 and several other antioxidant enzymes or cytoprotective proteins induced by 15d-PGJ2 is, in large part, regulated by its direct modification of Keap1 to form a covalently bound adduct and the subsequent activation of the ARE/EpRE.”
BackgroundMethodInfluentialPleiotropic effects of oxidized phospholipids
Bochkov, V. N., Gesslbauer, B., Mauerhofer, C., Philippova, M., Erné, P., & Oskolkova, O. (2016) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2016.12.034 · Cited by 129
Self-defense of macrophages against oxidative injury: Fighting for their own survival
Virág, L., Jaén, R. I., Regdon, Z., Boscá, L., & Prieto, P. (2019) · Redox Biology · doi:10.1016/j.redox.2019.101261 · Cited by 121
Metadata
- Authors
- Itoh, K., Mochizuki, M., Ishii, Y., Ishii, T., Shibata, T., Kawamoto, Y., Kelly, V., Sekizawa, K., Uchida, K., & Yamamoto, M.
- Affiliations
- Life Science Center for Survival Dynamics, Tsukuba Advanced Research Alliance (TARA) (JP)
- Institute of Clinical Medicines
- University of Tsukuba (JP)
- Nagoya University (JP)
- Institute of Social Medicines, University of Tsukuba, Tsukuba 305-8577
- Corresponding author
- Yamamoto, Masayuki
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2004-01-01
- Volume
- 24
- Issue
- 1
- Pages
- 36-45
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC303336
- OpenAlex
- W2113971187
- Cited by
- 407
- References
- 46
- Citations by year
- 2026: 4 · 2025: 8 · 2024: 9 · 2023: 13 · 2022: 13 · 2021: 21 · 2020: 20 · 2019: 20 · 2018: 21 · 2017: 21 · 2016: 24 · 2015: 23 · 2014: 14 · 2013: 21 · 2012: 11
- FWCI
- 6.55
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Molecular and Cellular Biology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics, phytochemicals, and oxidative stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Heme Oxygenase-1 and Carbon Monoxide
- Health Sciences › Medicine › Pharmacology (medical) › Inflammatory mediators and NSAID effects
- Keywords
- Nrf2, 15-deoxy-Δ12,14-prostaglandin J2, anti-inflammatory signaling, macrophages, neutrophil recruitment, carrageenan-induced pleurisy, Keap1, heme oxygenase-1, peroxiredoxin 1, cyclooxygenase-2, NS-398, acute inflammation, Nrf2-deficient mice
- MeSH terms
- Animals, DNA-Binding Proteins, Inflammation, Isoenzymes, Macrophages, Peritoneum, Pleurisy, Prostaglandin-Endoperoxide Synthases, Prostaglandin D2, Trans-Activators, Hepatocytes, NF-E2-Related Factor 2, Mice, Cyclooxygenase 2
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
