Abstract
Objective-The aim of this study was to determine the effects of oxidized versus native omega-3 fatty acids on the endothelial expression of chemokines MCP-1 and IL-8, and, if effective in inhibiting chemokine expression, to determine the mechanism for the inhibition of chemokine expression. Methods and Results-Using enzyme-linked immunosorbent assays, we show that oxidized EPA and DHA but not unoxidized EPA or DHA inhibit cytokine-induced endothelial expression of monocyte chemoattractant protein (MCP)-1 and, to a lesser extent, IL-8. In electrophoretic mobility shift assays, oxidized EPA but not unoxidized EPA potently inhibited cytokine-induced activation of endothelial nuclear factor-κB (NF-κB). Using Western blot analyses, we show that the inhibition of NF-κB activation was not caused by prevention of phosphorylation of IκBα because oxidized EPA did not inhibit cytokine-induced phosphorylation and ubiquination of IκBα. Furthermore, oxidized EPA inhibited NF-κB activation in endothelial cells derived from wild-type mice but had no inhibitory effects on NF-κB activation in endothelial cells derived from peroxisome proliferator-activated receptor α (PPARα)-deficient mice, indicating that oxidized EPA requires PPARα for its inhibitory effects on NF-κB. Conclusions-These studies show that the antiinflammatory effects of fish oil may result from the inhibitory effects of oxidized omega-3 fatty acids on NF-κB activation via a PPARα-dependent pathway.
Original language | English (US) |
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Pages (from-to) | 1621-1627 |
Number of pages | 7 |
Journal | Arteriosclerosis, thrombosis, and vascular biology |
Volume | 24 |
Issue number | 9 |
DOIs | |
State | Published - Sep 2004 |
Keywords
- Monocyte chemoattractant protein-1
- Nuclear factor-κB
- Oxidized eicosapentaenoic acid
- Oxidized omega-3 fatty acids
- PPARa
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine