Influence of oxidized low-density lipoprotein on siglec-1 expression and cytokine secretion by U937 cells
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Supported by National High-tech R&D Program (“863” Program,2006AA02Z496) and Excellent Leading Scientist Foundation of Shanghai Science and Technology Committee(07XD14013).
Objective:To explore the role of sialic acid-binding immunoglobulin-like lectin-one (Siglec-1) in oxidized low-density lipoprotein (ox-LDL)-induced atherosclerotic inflammation.Methods:Ox-LDL was prepared by oxidization of native LDL;different concentrations of ox-LDL were used to treat U937 cells for 48 h.Cells and supernatants were collected.The expression of Siglec-1 protein and mRNA was examined by flow cytometry (FCM) and real-time quantitative RT-PCR,respectively.The levels of MIP-1α,MCP-1 and IL-8 in the supernatants were determined by ELISA.Results:Stimulation with ox-LDL significantly increased Siglec-1 protein and mRNA in U937 cells compared with the control group(P<0.01).Meanwhile,the levels of MIP-1α,MCP-1 and IL-8 in the supernatants were also significantly increased in a concentration-dependent manner compared with those in the control group(P<0.01).Conclusion:The proatherogenic effect of ox-LDL may be partly through up-regulating Siglec-1 expression in macrophages and enhancing the expression of inflammatory cytokines and chemokines.The activated macrophages recruit more macrophages and lymphocytes to the site of atherosclerotic plaques and exacerbate the inflammatory responses.