The omega-3 fatty acid docosahexaenoate attenuates endothelial cyclooxygenase-2 induction through both NADP(H) oxidase and PKCĪµ inhibition Academic Article uri icon


MeSH Major

  • Cyclooxygenase 2
  • Docosahexaenoic Acids
  • Endothelium, Vascular
  • NADPH Oxidase
  • Protein Kinase C-epsilon


  • A high intake of the omega-3 fatty acid docosahexaenoate [docosahexaenoic acid (DHA)] has been associated with systemic antiinflammatory effects and cardiovascular protection. Cyclooxygenase (COX)-2 is responsible for the overproduction of prostaglandins (PG) at inflammatory sites, and its expression is increased in atheroma. We studied the effects of DHA on COX-2 expression and activity in human saphenous vein endothelial cells challenged with proinflammatory stimuli. A>or=24-h exposure to DHA reduced COX-2 expression and activity induced by IL-1, without affecting COX-1 expression. DHA effect depended on the NF-kappaB-binding site in the COX-2 promoter. EMSAs confirmed that DHA attenuated NF-kappaB activation. Because MAPK, PKC, and NAD(P)H oxidase all participate in IL-1-mediated COX-2 expression, we also tested whether these enzymes were involved in DHA effects. Western blots showed that DHA blocked nuclear p65 NF-kappaB subunit translocation by decreasing cytokine-stimulated reactive oxygen species and ERK1/2 activation by effects on both NAD(P)H oxidase and PKCepsilon activities. Finally, to address the question whether DHA itself or DHA-derived products were responsible for these effects, we inhibited the most important enzymes involved in polyunsaturated fatty acid metabolism, showing that 15-lipoxygenase-1 products mediate part of DHA effects. These studies provide a mechanistic basis for antiinflammatory and possibly plaque-stabilizing effects of DHA.

publication date

  • October 10, 2006



  • Academic Article



  • eng

PubMed Central ID

  • PMC1622797

Digital Object Identifier (DOI)

  • 10.1073/pnas.0510086103

PubMed ID

  • 17018645

Additional Document Info

start page

  • 15184

end page

  • 9


  • 103


  • 41