Docosahexaenoic acid attenuates VCAM-1 expression and NF-kappa B activation in TNF-alpha-treated human aortic endothelial cells

作者：Wang Tzu Ming; Chen Chun Jung; Lee Tzong Shyuan; Chao Han Yi; Wu Wen Huey; Hsieh Shu Chen; Sheu Huey Herng; Chiang An Na^*

来源：Journal of Nutritional Biochemistry, 2011, 22(2): 187-194.

DOI：10.1016/j.jnutbio.2010.01.007

• Docosahexaenoic acid
• Polyunsaturated fatty acids
• apoE knockout mice
• VCAM-1
• ICAM-1
• Human aortic endothelial cells

This study was conducted to test the hypothesis that n-3 polyunsaturated fatty acids are able to down-regulate expression of adhesion molecules and nuclear factor-kappa B (NF-kappa B) activation in vascular endothelial cells, in addition to reducing atherosclerotic lesions in vivo. We report here that docosahexaenoic acid (DHA) reduces atherosclerotic lesions in the aortic arteries of apolipoprotein E knockout (apoE(-/-)) mice. Consistent with the observation in animal study, DHA inhibited THP-1 cell adhesion to tumor necrosis factor alpha (INF-alpha)-activated human aortic endothelial cells (HAECs). Expression of vascular cell adhesion molecule 1 (VCAM-1) and intercellular adhesion molecule 1 (ICAM-1) on the cell surface of HAECs was determined by cell-surface enzyme-linked immunosorbent assay. DHA and eicosapentaenoic acid decreased VCAM-1 expression in a dose-dependent manner in TNF-alpha treated HAECs, while cis-linoleic acid and arachidonic acid did not have any significant effect on either VCAM-1 or ICAM-1 expression. Moreover, DHA significantly reduced VCAM-1 protein expression in the cell lysates of TNF-alpha-treated HAECs, as determined by Western blot analysis. In line with NF-kappa B signaling pathway, DHA suppressed the TNF-alpha-activated I kappa B alpha phosphorylation and degradation as well as I kappa B kinase-beta phosphorylation. Subsequently, translocation of the NF-kappa B (p50/p65) and AP-1 (c-Fos/c-Jun) subunits was down-regulated by DHA in the nucleus of HAECs. These results suggest that DHA negatively regulates TNF-alpha-induced VCAM-1 expression through attenuation of NF-kappa B signaling pathway and AP-1 activation. This study provides evidence that DHA may contribute to the prevention of atherosclerosis and inflammatory diseases in vivo.

• 出版日期2011-2