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.
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“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]
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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
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