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National Institute of Environmental Health Sciences

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Your Environment. Your Health.

Publication Detail

Title: Role of Nrf2 in suppressing LPS-induced inflammation in mouse peritoneal macrophages by polyunsaturated fatty acids docosahexaenoic acid and eicosapentaenoic acid.

Authors: Wang, Hu; Khor, Tin Oo; Saw, Constance Lay Lay; Lin, Wen; Wu, Tienyuan; Huang, Ying; Kong, Ah-Ng Tony

Published In Mol Pharm, (2010 Dec 06)

Abstract: This study is to investigate the role of Nrf2 in suppressing LPS-mediated inflammation in ex vivo macrophages by polyunsaturated fatty acids (PUFA) docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). Primary peritoneal macrophages from Nrf2 wild-type (+/+; WT) and Nrf2 knockout (-/-; KO) mice were treated with lipopolysaccharides (LPS) in the presence or absence of DHA or EPA. Quantitative real-time PCR (qPCR) analyses showed that LPS potently induced cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) in the macrophages collected from Nrf2 (+/+) wild-type mice. DHA and EPA inhibited LPS-induced COX-2, iNOS, IL-1β, IL-6, or TNF-α, but increased hemeoxygenase (HO-1) expression. DHA was found to be more potent than EPA in inhibiting COX-2, iNOS, IL-1β, IL-6, and TNF-α mRNA expression. DHA and EPA were also found to induce HO-1 and Nrf2 mRNA with a different dose-response. LPS induced COX-2, iNOS, IL-1β, IL-6, and TNF-α in the macrophages collected from Nrf2 (-/-) mice as well, however, DHA and EPA suppression of COX-2, iNOS, IL-1β, IL-6, and TNF-α was attenuated as compared to that in Nrf2 (+/+) macrophages. Taken together, using Western blotting, ELISA and qPCR approaches coupled with Nrf2 (-/-) mice, our study clearly shows for the first time that DHA/EPA would induce Nrf2 signaling pathway and that Nrf2 plays a role in DHA/EPA suppression of LPS-induced inflammation.

PubMed ID: 20831192 Exiting the NIEHS site

MeSH Terms: Animals; Cyclooxygenase 2/genetics; Cyclooxygenase 2/metabolism; Docosahexaenoic Acids/pharmacology*; Eicosapentaenoic Acid/pharmacology*; Heme Oxygenase-1/antagonists & inhibitors; Heme Oxygenase-1/genetics; Heme Oxygenase-1/metabolism; Inflammation/chemically induced; Inflammation/prevention & control*; Interleukin-6/antagonists & inhibitors; Interleukin-6/genetics; Interleukin-6/secretion; Lipopolysaccharides/antagonists & inhibitors; Lipopolysaccharides/pharmacology; Macrophages, Peritoneal/drug effects; Macrophages, Peritoneal/metabolism*; Mice; Mice, Inbred C57BL; Mice, Knockout; NF-E2-Related Factor 2/deficiency; NF-E2-Related Factor 2/metabolism*; Nitric Oxide Synthase Type II/antagonists & inhibitors; Nitric Oxide Synthase Type II/genetics; Nitric Oxide Synthase Type II/metabolism; Nitrites/metabolism; Reverse Transcriptase Polymerase Chain Reaction; Structure-Activity Relationship; Tumor Necrosis Factor-alpha/antagonists & inhibitors; Tumor Necrosis Factor-alpha/genetics; Tumor Necrosis Factor-alpha/secretion

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