Docosahexaenoic acid decreases TNF-α-induced lectin-like oxidized low-density lipoprotein receptor-1 expression in THP-1 cells.

ABSTRACT

Docosahexaenoic acid (DHA) prevents atherosclerosis and may decrease monocyte/macrophage activation by tumor necrosis factor (TNF)-α. Here, we sought to determine the protective effects of DHA against TNF-α-induced stimulation of lectin-like oxidized low-density lipoprotein (LDL) receptor-1 (LOX-1) expression, which is associated with atherosclerosis. Using reverse transcription polymerase chain reaction, we found that TNF-α induced the expression of LOX-1 (OLR1), NADPH oxidase 2 (Nox2), p47phox (NCF1), very late antigen-4 (ITGA4), and lymphocyte function-associated antigen (ITGAL) genes. Additionally, DHA attenuated TNF-α-induced acetylated (Ac)-LDL uptake and reactive oxygen species (ROS) production, as measured using fluorescently labeled LDL and H2DCFDA, respectively, and reduced the expression levels of these genes. Moreover, the PI3 kinase inhibitor LY294002 blocked these effects of DHA. These results indicated that DHA inhibited several events associated with redox regulation in a PI3K-dependent manner, thereby mediating the expression of LOX-1 in monocytes/macrophages.