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N‐3 polyunsaturated fatty acids prevent production/activation of pro‐inflammatory mediators
Author(s) -
Chen Linda H,
Zhao Yan
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a605-b
Subject(s) - thromboxanes , leukotriene b4 , polyunsaturated fatty acid , tumor necrosis factor alpha , docosahexaenoic acid , eicosapentaenoic acid , arachidonic acid , chemistry , thromboxane a2 , cytokine , proinflammatory cytokine , inflammation , pharmacology , biochemistry , endocrinology , fatty acid , biology , immunology , receptor , enzyme
Tumor necrosis factor‐α (TNF‐α) is an endotoxin (lipopolysaccharide, LPS)‐inducible cytokine that plays an important role in the inflammatory processes. TNF‐α is implicated in the pathobiology of many human diseases such as rheumatoid arthritis. Inhibition of elevated TNF‐α levels has been proposed as a strategy for preventing the progression of these diseases. Eicosanoids derived from arachidonic acid (ARA) such as leukotrienes and thromboxanes have been implicated in the inflammatory responses. Transcription factors, nuclear factor‐κB (NF‐κB) and activator protein‐1 (AP‐1), regulate the expression of TNF‐α gene. In this study, the effects of n‐3 polyunsaturated fatty acids (PUFAs) on pro‐inflammatory mediators including TNF‐α, certain eicosanoids, NF‐κB and AP‐1 were investigated in human monocytic THP‐1 cells. The results showed that N‐3 PUFAs, eicosapentaenoic acid (EPA, C 20:5 ) and docosahexaenoic acid (DHA, C 22:6 ), decreased the production of TNF‐α to the greatest extent among various fatty acids. Levels of pro‐inflammatory eicosanoids generated from ARA, thromboxane B 2 (TXB 2 ) and leukotriene B 4 (LTB 4 ), were inhibited by EPA pre‐incubation. Suppressing the production of these eicosanoids by lipoxygenase inhibitor and thromboxane synthase inhibitors decreased TNF‐α production. Furthermore, LPS‐stimulated activation of NF‐κB and AP‐1 was prevented by EPA pre‐treatment of cells. Our findings suggest that N‐3 PUFAs partly inhibit TNF‐α production through replacing ARA in membrane lipids and decreasing pro‐inflammatory eicosanoids derived from ARA. Our results also suggest that n‐3 PUFAs partly suppress TNF‐α production by preventing the activation of transcription factors, NF‐κB and AP‐1. Supported by Kentucky Agricultural Experiment Station.