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• W2113971187 abstract "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-Δ 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." @default.
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• W2113971187 date "2004-01-01" @default.
• W2113971187 modified "2023-10-11" @default.
• W2113971187 title "Transcription Factor Nrf2 Regulates Inflammation by Mediating the Effect of 15-Deoxy-Δ ^12,14 -Prostaglandin J ₂" @default.
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• W2113971187 doi "https://doi.org/10.1128/mcb.24.1.36-45.2004" @default.
• W2113971187 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/303336" @default.
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