Silencing Triggering Receptors Expressed on Myeloid Cells-1 Impaired the Inflammatory Response to Oxidized Low-Density Lipoprotein in Macrophages.
Atherosclerosis is a chronic progressive inflammatory disease characterized by the accumulation of lipid contents in arterial walls. Previous studies suggest participation of Toll-like receptors (TLRs) in lipid deposition and inflammatory response in vascular wall. The triggering receptor expressed on myeloid cells 1 (TREM-1) is a cell surface receptor of the immunoglobulin superfamily, which amplifies signal transduction of TLR pathway and enhances immune response to microbial infections. The aim of the present study was to investigate the effect of the oxidized low-density lipoprotein (oxLDL) on the expression of the TREM-1, as well as its engagement in proinflammatory cytokine production and foam cell formation in RAW264.7 mice macrophages. oxLDL enhanced TREM-1 and TLR-4, but not TLR-2 gene expression in macrophages; furthermore, silencing TREM-1 expression by short hairpin interfering RNA inhibited lipid phagocytosis and proinflammatory tumor necrosis factor-α (TNF-α) as well as interleukin-6 (IL-6) production in macrophages; moreover, application of synthetic antagonist, LP-17 polypeptide, reduced IL-6 production upon oxLDL stimulation in vitro and in vivo. In conclusion, in macrophages, oxLDL enhanced expression of TREM-1, which amplifies the innate immune response of TLR pathway; activation of TREM-1 contributes to atherogenesis process by enhancing proinflammatory cytokine production and foam cell formation.
Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, 210008, China.
Houxuan
H
Li
Department of Periodontology, Xiamen Stomatological Hospital, Xiamen, Fujian, 361000, China.
Feifei
F
Hong
Department of Periodontology, Xiamen Stomatological Hospital, Xiamen, Fujian, 361000, China.
Shengbo
S
Pan
Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, 210008, China. leilangdental@163.com.
Lang
L
Lei
Nanjing Stomatological Hospital, Medical School of Nanjing University, Nanjing, Jiangsu, 210008, China. fhyan2005@126.com.
Fuhua
F
Yan
D000818:Animals; D050197:Atherosclerosis / Q000276:immunology* / Q000473:pathology; D002460:Cell Line; D004730:Endothelium, Vascular / Q000276:immunology*; D005487:Foam Cells; D007113:Immunity, Innate / Q000276:immunology; D007249:Inflammation / Q000139:chemically induced / Q000276:immunology; D015850:Interleukin-6 / Q000096:biosynthesis; D066292:Lipid Droplets / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000009:adverse effects*; D008264:Macrophages / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology*; D051379:Mice; D010084:Oxidation-Reduction; D010587:Phagocytosis / Q000235:genetics; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology*; D015398:Signal Transduction / Q000276:immunology; D051195:Toll-Like Receptor 2 / Q000096:biosynthesis / Q000276:immunology; D051197:Toll-Like Receptor 4 / Q000096:biosynthesis / Q000276:immunology; D000073871:Triggering Receptor Expressed on Myeloid Cells-1; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D015850:Interleukin-6; D008077:Lipoproteins, LDL; D008562:Membrane Glycoproteins; D034741:RNA, Small Interfering; D011971:Receptors, Immunologic; C495342:TLR2 protein, human; C495345:TLR4 protein, human; C517262:TREM1 protein, mouse; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D000073871:Triggering Receptor Expressed on Myeloid Cells-1; D014409:Tumor Necrosis Factor-alpha; C099252:oxidized low density lipoprotein
Toll-like receptors; macrophages, atherosclerosis; oxidized low-density lipoprotein; triggering receptors expressed on myeloid cells-1