Docosahexaenoic Acid Selectively Attenuates Induction of Vascular Cell Adhesion Molecule–1 and Subsequent Monocytic Cell Adhesion to Human Endothelial Cells Stimulated by Tumor Necrosis Factor–α

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Abstract
Incorporation of the n-3 polyunsaturated fatty acid docosahexaenoic acid (DHA) but not eicosapentaenoic acid or n-6 arachidonic acid into human umbilical vein endothelial cell (HUVEC) phospholipids dose-dependently reduced tumor necrosis factor–α (TNF-α)–induced surface expression of vascular cell adhesion molecule–1 (VCAM-1). In parallel, DHA inhibited TNF-α–stimulated monocytic U937 cell adhesion to HUVECs but did not affect TNF-α– or interferon gamma–induced expression of intercellular adhesion molecule–1 and endothelial leukocyte adhesion molecule–1 or VCAM-1 induction by interleukin-1β. DHA appeared to attenuate VCAM-1 transcription, as it reduced induction of VCAM-1 mRNA by TNF-α. VCAM-1 induction is regulated by activation of nuclear factor–kB, which can be mediated by a TNF-α–responsive phosphatidylcholine-specific phospholipase C (PC-PLC). Gel-shift analysis showed inhibition of TNF-α–induced nuclear factor–kB mobilization by DHA. While the PC-PLC inhibitor D609 dose-dependently prevente...