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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2004;24:1621.)
© 2004 American Heart Association, Inc.

Vascular Biology

Oxidized Omega-3 Fatty Acids Inhibit NF-B Activation Via a PPAR-Dependent Pathway

Archana Mishra; Ashok Chaudhary; Sanjeev Sethi

From the Department of Pathology, University of Iowa Hospitals and Clinics, Iowa City, Iowa.

Correspondence to Dr Sanjeev Sethi, Department of Pathology, 5243 RCP, University of Iowa Hospitals and Clinics, 200 Hawkins Drive, Iowa City, IA 52242. E-mail sanjeev-sethi{at}uiowa.edu

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-B (NF-B). Using Western blot analyses, we show that the inhibition of NF-B activation was not caused by prevention of phosphorylation of IB because oxidized EPA did not inhibit cytokine-induced phosphorylation and ubiquination of IB. Furthermore, oxidized EPA inhibited NF-B activation in endothelial cells derived from wild-type mice but had no inhibitory effects on NF-B activation in endothelial cells derived from peroxisome proliferator-activated receptor (PPAR)-deficient mice, indicating that oxidized EPA requires PPAR for its inhibitory effects on NF-B.

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-B activation via a PPAR-dependent pathway.

Key Words: monocyte chemoattractant protein-1 • oxidized omega-3 fatty acids • oxidized eicosapentaenoic acid • nuclear factor-B • PPARa

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