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• W2150063586 abstract "Abstract Modulation of monocyte function is a critical factor in the resolution of inflammatory responses. This role is mediated mainly by the production of TNF-α. Investigations of the actions of TNF have mostly focused on acute activation of other cell types such as fibroblasts and endothelial cells. Less is known about the effects of TNF on monocytes themselves, and little is known about the regulation of cell responses to TNF beyond the activation of NF-κB. In this study, we investigated the regulation of NF-E2–related factor 2 (Nrf2) cyctoprotective responses to TNF in human monocytes. We found that in monocytes TNF induces sustained Nrf2 activation and Nrf2 cytoprotective gene induction in a TNFR1-dependent manner. Under TNF activation, monocytes increased their expression of Nrf2-dependent genes, including NAD(P)H:quinone oxidoreductase 1 and glutamyl cysteine ligase modulatory, but not heme oxygenase-1. We also showed that autocrine TNF secretion was responsible for this sustained Nrf2 response and that Nrf2 activation by TNF was mediated by the generation of reactive oxygen species. Moreover, we showed that Nrf2-mediated gene induction can modulate TNF-induced NF-κB activation. These results show for the first time, to our knowledge, that TNF modulates prolonged Nrf2-induced gene expression, which in turn regulates TNF-induced inflammatory responses." @default.
• W2150063586 created "2016-06-24" @default.
• W2150063586 creator A5005954344 @default.
• W2150063586 creator A5051775909 @default.
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• W2150063586 date "2011-07-15" @default.
• W2150063586 modified "2023-10-18" @default.
• W2150063586 title "TNF Mediates the Sustained Activation of Nrf2 in Human Monocytes" @default.
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• W2150063586 doi "https://doi.org/10.4049/jimmunol.1004117" @default.
• W2150063586 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/21670314" @default.
• W2150063586 hasPublicationYear "2011" @default.
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