出版社：American Society for Biochemistry and Molecular Biology
摘要：LPL and endothelial lipase (EL) are associated with macrophagesin human atherosclerotic lesions, and overexpression of LPLin mouse macrophages is associated with a greater extent ofatherosclerosis. To investigate potential mechanisms by whichmacrophage-derived lipase expression may mediate proatherogeniceffects, we used lentivirus-mediated RNA interference to suppressthe expression of either LPL or EL within THP-1 macrophages.After suppression of either LPL or EL, significant decreasesin the concentration of interleukin-1ß, interleukin-6,monocyte chemoattractant protein-1, and tumor necrosis factor-were observed. Incubation of THP-1 macrophages with either mildlyor extensively oxidized LDL consistently decreased cytokineexpression, which was additive to that contributed by lipasesuppression. Decreased lipase expression was also associatedwith an altered lipid composition, with reduced percentagesof cholesterol (unesterified and esterified), triglycerides,and lysophosphatidylcholine. Microarray data indicated a decreasedexpression of proinflammatory genes, growth factors, and antiapoptoticgenes. By contrast, there was an increased expression of lipoproteinreceptors (scavenger receptor 1, low density lipoprotein receptor,scavenger receptor class B type I, and CD36). Thus, we concludethat the suppression of either LPL or EL decreases proinflammatorycytokine expression and influences the lipid composition ofTHP-1 macrophages. These results provide further insight intothe specific metabolic and potential pathological roles of LPLand EL in human macrophages.Supplementary key words monocyte • inflammation • microarray • RNA interference • lentivirus
Abbreviations: EL, endothelial lipase; IL, interleukin; lyso-PC, lysophosphatidylcholine; MCP-1, monocyte chemoattractant protein-1; MOI, multiplicity of infection; NF-B, nuclear factor-B; OxLDL, oxidized low density lipoprotein; PMA, phorbol 12-myristate 13-acetate; PPAR, peroxisome proliferator-activated receptor ; TBARS, thiobarbituric acid-reacting substances; TNF-, tumor necrosis factor-
were observed. Incubation of THP-1 macrophages with either mildly or extensively oxidized LDL consistently decreased cytokine expression, which was additive to that contributed by lipase suppression. Decreased lipase expression was also associated with an altered lipid composition, with reduced percentages of cholesterol (unesterified and esterified), triglycerides, and lysophosphatidylcholine. Microarray data indicated a decreased expression of proinflammatory genes, growth factors, and antiapoptotic genes. By contrast, there was an increased expression of lipoprotein receptors (scavenger receptor 1, low density lipoprotein receptor, scavenger receptor class B type I, and CD36). Thus, we conclude that the suppression of either LPL or EL decreases proinflammatory cytokine expression and influences the lipid composition of THP-1 macrophages. These results provide further insight into the specific metabolic and potential pathological roles of LPL and EL in human macrophages.
Supplementary key words monocyte • inflammation • microarray • RNA interference • lentivirus
Abbreviations: EL, endothelial lipase; IL, interleukin; lyso-PC, lysophosphatidylcholine; MCP-1, monocyte chemoattractant protein-1; MOI, multiplicity of infection; NF-
B, nuclear factor-
, peroxisome proliferator-activated receptor 
