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Anti-inflammatory effects of oxidized omega-3 fatty acids are mediated through inhibition of NF- kappa B via a PPAR alpha dependent pathway

Anti-inflammatory effects of oxidized omega-3 fatty acids are mediated through inhibition of NF- kappa B via a PPAR alpha dependent pathway

FASEB Journal 18(4-5): Abstract 44

ISSN/ISBN: 0892-6638

Omega-3 fatty acids, like eicosapentaenoic acid (EPA), are highly polyunsaturated and readily undergo autooxidation. EPA was auto-oxidized by incubating EPA (3.3mM) in PBS at 37degreesC for 16 hours. By ELISA methods we show that oxidized EPA, in a dose dependent manner, but not unoxidized EPA, inhibits TNFα and IL-1β induced endothelial expression of MCP-1, and to a lesser extent IL-8. In gel shift assays, oxidized EPA (100μM) potently inhibited cytokine induced activation of NF-κB but had no significant inhibitory effect on AP-1 activation. Unoxidized EPA had no effect on either NF-κB or AP-1 activation. The inhibition of NF-κB activation was not due to prevention of phosphorylation of IkBα since western blot analyses showed that oxidized EPA did not inhibit cytokine induced phosphorylation and ubiquination of IkBα. Furthermore, oxidized EPA inhibited cytokine induced NF-κB activation in microvessels derived from wild-type mice but had no inhibitory effect on NF-κB in microvessels derived from PPARα-/- deficient mice indicating that oxidized EPA requires PPARα for its inhibitory effect on NF-κB. These studies show that the anti-inflammatory 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.

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Accession: 034415598

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