Submitted on July 13, 2006
Revised on October 23, 2006
Accepted on November 7, 2006
Suppression of endothelial lipase or lipoprotein lipase expression in THP-1 macrophages attenuates pro-inflammatory cytokine secretion
Guosong Qiu, Alexander C. Ho, Willie Yu, and John S. Hill
Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC V6Z 1Y6
Corresponding Author: jshill{at}interchange.ubc.ca
Lipoprotein lipase (LPL) and endothelial lipase (EL) are associated with macrophages in human atherosclerotic lesions and overexpression of LPL in mouse macrophages is associated with a greater extent of atherosclerosis. To investigate potential mechanisms by which macrophage-derived lipase expression may mediate proatherogenic effects, we used lentiviral-mediated RNA interference to suppress the expression of either LPL or EL within THP-1 macrophages. Following suppression of either LPL or EL, significant decreases in the concentration of IL-1ß, IL-6, MCP-1, and TNF-a 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 (SRA, LDLR, SR-BI, and CD36). Taken together, 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.
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