Role of Nrf2 in Suppressing LPS-Induced Inflammation in Mouse Peritoneal Macrophages by Polyunsaturated Fatty Acids Docosahexaenoic Acid and Eicosapentaenoic Acid

被引:103
|
作者
Wang, Hu [1 ]
Khor, Tin Oo [2 ]
Saw, Constance Lay Lay [2 ]
Lin, Wen [1 ]
Wu, Tienyuan [1 ]
Huang, Ying [1 ]
Kong, Ah-Ng Tony [1 ,2 ]
机构
[1] Rutgers State Univ, Ernest Mario Sch Pharm, Grad Program Pharmaceut Sci, Dept Pharmaceut, Piscataway, NJ 08854 USA
[2] Rutgers State Univ, Ernest Mario Sch Pharm, Ctr Canc Prevent Res, Dept Pharmaceut, Piscataway, NJ 08854 USA
关键词
Docosahexaenoic acid; eicosapentaenoic acid; nuclear factor-erythroid 2-related factor 2; Nrf2; inflammation; antioxidative stress; HEME OXYGENASE-1 INDUCTION; GENE-EXPRESSION; NITRIC-OXIDE; HYPOCHLOROUS ACID; CELL-SURVIVAL; FISH-OIL; CANCER; ACCUMULATION; MODULATION; PATHWAY;
D O I
10.1021/mp100199m
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
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.
引用
收藏
页码:2185 / 2193
页数:9
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