Over‐expression of 12/15‐lipoxygenase increases oxLDL‐induced pro‐inflammatory mediator expression and foam cell formation in rodent macrophages

Blueberries (BB) prevent the development of atherosclerosis in apoE deficient mice, partly through suppressing 12/15‐lipoxygenase (12/15‐LOX) expression and reducing the production of oxidized lipid products. To further study the role of 12/15‐LOX in atherosclerosis and investigate the inhibitory effects of BB, a rodent macrophage cell line RAW264.7 was transfected with the 12/15‐LOX gene to investigate over‐expression of this enzyme on oxLDL‐induced inflammatory mediator production and foam cell formation. Over‐expression of 12/15‐LOX increased gene expression of the pro‐inflammatory mediators TNF‐α, RANTES and MIP in macrophage stimulated with oxLDL, which was accompanied by increased NF‐κB activity as measured by a SEAP reporter assay. When induced by oxLDL, over‐expression of 12/15‐LOX showed increased gene expression of two scavenger receptors (CD36 and SR‐A) and the reduction of two ATP‐binding cassette transporters (ABCA1 and ABCG1) expression. When assessed with Oil Red O staining, foam cell formation was increased in macrophages that over‐expressed 12/15‐LOX. Our data suggest that over‐expression of 12/15‐LOX contributes to a pro‐atherogenic phenotype. Further investigations of mechanisms underlying suppression of 12/15‐LOX by BB feeding are in progress. (USDA‐CRIS‐6251‐5100002‐06S)