Cited by 407Genomics, phytochemicals, and oxidative stressHeme Oxygenase-1 and Carbon MonoxideInflammatory mediators and NSAID effects

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Transcription Factor Nrf2 Regulates Inflammation by Mediating the Effect of 15-Deoxy-Δ12,14-Prostaglandin J2

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Itoh, Ken, Mochizuki, Mie, Ishii, Yukio, Ishii, Tetsuro, Shibata, Takahiro, Kawamoto, Yoshiyuki, Kelly, Vincent, Sekizawa, Kiyohisa, Uchida, Koji, Yamamoto, Masayuki·2004·Molecular and Cellular Biology

DOI 10.1128/mcb.24.1.36-45.2004PMC PMC303336

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Abstract

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.

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VANE, J. R. (1971) · Nature New Biology · doi:10.1038/newbio231232a0 · Cited by 8,605
An Nrf2/Small Maf Heterodimer Mediates the Induction of Phase II Detoxifying Enzyme Genes through Antioxidant Response Elements
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
Keap1 represses nuclear activation of antioxidant responsive elements by Nrf2 through binding to the amino-terminal Neh2 domain
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-citation
The 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
Direct evidence that sulfhydryl groups of Keap1 are the sensors regulating induction of phase 2 enzymes that protect against carcinogens and oxidants
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-citation
Pharmacological and biochemical demonstration of the role of cyclooxygenase 2 in inflammation and pain.
Seibert, 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
Nonsteroid drug selectivities for cyclo-oxygenase-1 rather than cyclo-oxygenase-2 are associated with human gastrointestinal toxicity: A full in vitro analysis
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
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Self-citation
Studies of the mediators of the acute inflammatory response induced in rats in different sites by carrageenan and turpentine
Rosa, M. D., Giroud, J. P., & Willoughby, D. A. (1971) · The Journal of Pathology · doi:10.1002/path.1711040103 · Cited by 1,409
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Rossi, A., Kapahi, P., Natoli, G., Takahashi, T., Chen, Y., Karin, M., & Santoro, M. G. (2000) · Nature · doi:10.1038/47520 · Cited by 1,303
Inducible cyclooxygenase may have anti-inflammatory properties
Gilroy, D. W., Colville‐Nash, P., Willis, D., Chivers, J. E., Paul‐Clark, M. J., & Willoughby, D. A. (1999) · Nature Medicine · doi:10.1038/9550 · Cited by 1,242
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Self-citation
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Radjendirane, V., & Jaiswal, A. K. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.25.14960 · Cited by 1,034
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Itoh, K., Wakabayashi, N., Katoh, Y., Ishii, T., O'Connor, T., & Yamamoto, M. P. (2003) · Genes to Cells · doi:10.1046/j.1365-2443.2003.00640.x · Cited by 828
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Willis, D., Moore, A., Frederick, R., & Willoughby, D. A. (1996) · Nature Medicine · doi:10.1038/nm0196-87 · Cited by 782
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Enomoto, A. (2001) · Toxicological Sciences · doi:10.1093/toxsci/59.1.169 · Cited by 728
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Kang, S. W., Chae, H. Z., Seo, M. S., Kim, K., Baines, I., & Rhee, S. G. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.11.6297 · Cited by 693
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Cho, H., Jedlicka, A., Reddy, S. P., Kensler, T. W., Yamamoto, M. P., Zhang, L.-Y., & Kleeberger, S. R. (2002) · American Journal of Respiratory Cell and Molecular Biology · doi:10.1165/ajrcmb.26.2.4501 · Cited by 660
Self-citation
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Identification of a common chemical signal regulating the induction of enzymes that protect against chemical carcinogenesis.
Talalay, P., Long, M. J., & Prochaska, H. J. (1988) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.85.21.8261 · Cited by 595
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Roger, T., David, J. R., Glauser, M. P., & Calandra, T. (2001) · Nature · doi:10.1038/414920a · Cited by 586
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Chan, K., & Kan, Y. W. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.22.12731 · Cited by 574
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Lee, T., Tsai, H.-L., & Chau, L. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m300498200 · Cited by 212
Cloning and characterization of a 23-kDa stress-induced mouse peritoneal macrophage protein.
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Biological activities and mechanisms of action of PGJ2 and related compounds: an update
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[18] Roles of Nrf2 in activation of antioxidant enzyme genes via antioxidant responsive elements
Ishii, T., Itoh, K., & Yamamoto, M. P. (2002) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(02)48637-5 · Cited by 161
Self-citation
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Gong, P., Stewart, D., Hu, B., Li, N., Cook, J. L., Nel, A. E., & Alam, J. (2002) · Antioxidants and Redox Signaling · doi:10.1089/152308602753666307 · Cited by 139
Site and mechanism of growth inhibition by prostaglandins. III. Distribution and binding of prostaglandin A2 and delta 12-prostaglandin J2 in nuclei.
Narumiya, S., Ohno, K., Fukushima, M., & Fujiwara, M. (1987) · Journal of Pharmacology and Experimental Therapeutics · doi:10.1016/s0022-3565(25)39070-1 · Cited by 138
Induction of Cellular Antioxidative Stress Genes through Heterodimeric Transcription Factor Nrf2/Small Maf by Antirheumatic Gold(I) Compounds
Kataoka, K., Handa, H., & Nishizawa, M. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m105383200 · Cited by 125
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Primiano, T., Sutter, T. R., & Kensler, T. W. (1996) · Advances in pharmacology · doi:10.1016/s1054-3589(08)60989-8 · Cited by 112
Regulation of Macrophage Migration Inhibitory Factor and Thiol-specific Antioxidant Protein PAG by Direct Interaction
Jung, H., Kim, T., Chae, H. Z., Kim, K., & Ha, H. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m009620200 · Cited by 99
Role of Macrophage Migration Inhibitory Factor in the Regulation of the Immune Response
Metz, C. N., & Bucala, R. (1997) · Advances in immunology · doi:10.1016/s0065-2776(08)60598-2 · Cited by 91
Cyclopentenone prostaglandins—new allies in the war on inflammation
Willoughby, D. A., Moore, A., & Colville‐Nash, P. (2000) · Nature Medicine · doi:10.1038/72224 · Cited by 48
Biological actions of δ12-prostaglandin J2
Negishi, M., Koizumi, T., & Ichikawa, A. (1995) · Journal of Lipid Mediators and Cell Signalling · doi:10.1016/0929-7855(95)00029-p · Cited by 38

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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-citation
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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
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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

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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
ORCID: Itoh, Ken
Ishii, Yukio
Shibata, Takahiro
Kawamoto, Yoshiyuki
Kelly, Vincent
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
DOI: 10.1128/mcb.24.1.36-45.2004
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
Licence: journals.asm.org/non-commercial-tdm-license (tdm)
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

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Transcription Factor Nrf2 Regulates Inflammation by Mediating the Effect of 15-Deoxy-Δ12,14-Prostaglandin J2

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