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Over‐expression of 12/15‐lipoxygenase increases oxLDL‐induced pro‐inflammatory mediator expression and foam cell formation in rodent macrophages
Author(s) -
Thakali Keshari M,
Kang Jie,
Wu Xianli
Publication year - 2012
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.26.1_supplement.644.17
Subject(s) - cd36 , foam cell , scavenger receptor , abca1 , chemistry , arachidonate 5 lipoxygenase , inflammation , gene expression , mediator , reporter gene , transfection , microbiology and biotechnology , cell culture , macrophage , abcg1 , receptor , biology , arachidonic acid , biochemistry , gene , transporter , enzyme , immunology , cholesterol , in vitro , lipoprotein , genetics
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)