Oxidized omega-3 fatty acids inhibit NF-κB activation via a PPARα-dependent pathway

Archana Mishra, Ashok Chaudhary, Sanjeev Sethi

Research output: Contribution to journalArticle

163 Scopus citations

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 languageEnglish (US)
Pages (from-to)1621-1627
Number of pages7
JournalArteriosclerosis, thrombosis, and vascular biology
Volume24
Issue number9
DOIs
StatePublished - Sep 1 2004

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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

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