期刊
MOLECULAR PHARMACEUTICS
卷 7, 期 6, 页码 2185-2193出版社
AMER CHEMICAL SOC
DOI: 10.1021/mp100199m
关键词
Docosahexaenoic acid; eicosapentaenoic acid; nuclear factor-erythroid 2-related factor 2; Nrf2; inflammation; antioxidative stress
资金
- Institutional funds
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-1 beta), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-alpha) in the macrophages collected from Nrf2 (+/+) wild-type mice. DHA and EPA inhibited LPS-induced COX-2, iNOS, IL-1 beta, IL-6, or TNF-alpha, but increased hemeoxygenase (HO-1) expression. DHA was found to be more potent than EPA in inhibiting COX-2, iNOS, IL-1 beta, IL-6, and INF-alpha 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-1 beta, IL-6, and TNF-alpha in the macrophages collected from Nrf2 (-/-) mice as well, however, DHA and EPA suppression of COX-2, iNOS, IL-1 beta, IL-6, and TNF-alpha 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.
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