Anti-inflammatory effect of docosahexaenoic acid on cytokine-induced adhesion molecule expression in human retinal vascular endothelial cells

Invest Ophthalmol Vis Sci. 2005 Nov;46(11):4342-7. doi: 10.1167/iovs.05-0601.


Purpose: Docosahexaenoic acid (DHA(22:6n3)), the principal n3-polyunsaturated fatty acid (PUFA) in the retina, has been shown to have a pronounced anti-inflammatory effect in numerous in vivo and in vitro studies. Despite the importance of vascular inflammation in diabetic retinopathy, the anti-inflammatory role of DHA(22:6n3) in cytokine-stimulated human retinal vascular endothelial cells (hRVECs) has not been addressed.

Methods: Cytokine-induced expression of cell adhesion molecules (CAMs) was assessed by Western blot. The effect of DHA(22:6n3) on cytokine-induced nuclear factor (NF)-kappaB signaling was analyzed by Western blot analysis and electrophoretic mobility shift assay (EMSA).

Results: Stimulation of hRVECs with VEGF(165), TNFalpha, or IL-1beta for 6 to 24 hours caused significant induction of intracellular adhesion molecule (ICAM)-1 and vascular cell adhesion molecule (VCAM)-1 expression. Pretreatment of the cells with 100 microM of BSA-bound DHA(22:6n3) for 24 hours remarkably inhibited cytokine-induced CAM expression. IL-1beta, TNFalpha, and VEGF(165) induced nuclear translocation and binding of p65 and p50 NF-kappaB isoforms to the VCAM-1 promoter. DHA(22:6n3) pretreatment inhibited cytokine-induced NF-kappaB binding by 25% to 40%. Moreover, DHA(22:6n3) diminished IL-1beta induced phosphorylation of the inhibitor of nuclear factor (NF)-kappaB (I-kappaBalpha), thus preventing its degradation.

Conclusions: IL-1beta, TNFalpha, and VEGF(165) induced CAM expression in hRVECs through activation of the NF-kappaB pathway. DHA(22:6n3) inhibited cytokine induced CAM expression through suppression of NF-kappaB nuclear translocation and upstream I-kappaBalpha phosphorylation and degradation. DHA(22:6n3) could be an important anti-inflammatory agent in the face of increased cytokine production and CAM expression in the diabetic retina.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Blotting, Western
  • Cell Adhesion Molecules / metabolism*
  • Cytokines / pharmacology*
  • Docosahexaenoic Acids / pharmacology*
  • Electrophoresis, Polyacrylamide Gel
  • Electrophoretic Mobility Shift Assay
  • Endothelium, Vascular / drug effects*
  • Humans
  • Interleukin-1 / pharmacology
  • NF-kappa B / metabolism
  • Phosphorylation
  • Retinal Vessels
  • Tumor Necrosis Factor-alpha / pharmacology
  • Vascular Endothelial Growth Factor A / pharmacology


  • Cell Adhesion Molecules
  • Cytokines
  • Interleukin-1
  • NF-kappa B
  • Tumor Necrosis Factor-alpha
  • Vascular Endothelial Growth Factor A
  • Docosahexaenoic Acids