Chang, Shwu-FenShwu-FenChangPO-YUAN CHANGChou, Yuan-ChunYuan-ChunChouSHAO-CHUN LU2021-03-102021-03-102020-080360-3997https://scholars.lib.ntu.edu.tw/handle/123456789/551364In response to environmental stimuli, monocytes undergo polarization into classically activated (M1) or alternatively activated (M2) states. M1 and M2 macrophages exert opposing pro- and anti-inflammatory properties, respectively. Electronegative low-density lipoprotein (LDL) (LDL(-)) is a naturally occurring mildly oxidized LDL found in the plasma of patients with hypercholesterolemia, diabetes, and acute myocardial infarction, and has been shown to involve in the pathogenesis of atherosclerosis. In this study, we examined the effects of LDL(-) on macrophage polarization and the involvement of lectin-like oxidized LDL receptor-1 (LOX-1) in this process. THP-1 macrophages were treated with native LDL (nLDL) or LDL(-), and then the expression of M1/M2-related surface markers and cytokines were evaluated. The results show that treatment with LDL(-) resulted in profound increase in proinflammatory cytokines, IL-1β, IL-6, and TNF-α, and M1-surface marker CD86; however, M2-related cytokines, IL-10 and TGF-β, and M2-surface marker CD206 were not changed by LDL(-). Untreated or nLDL-treated cells were used as control. LDL(-)-induced M1 polarization and secretion of proinflammatory cytokines were diminished in LOX-1 knockdown cells. Taken together, the results show that LDL(-) promotes differentiation of human monocytes to M1 macrophages through a LOX-1-dependent pathway, and explore the contribution of LDL(-) and LOX-1 to the development of chronic inflammation in atherosclerosis.animationElectronegative LDL; LOX-1; Macrophage polarization[SDGs]SDG3cd206 antigen; CD86 antigen; interleukin 10; interleukin 1beta; interleukin 6; low density lipoprotein; lymphocyte antigen; messenger RNA; oxidized low density lipoprotein receptor 1; short hairpin RNA; transforming growth factor beta; tumor necrosis factor; unclassified drug; low density lipoprotein; OLR1 protein, human; oxidized low density lipoprotein; oxidized low density lipoprotein receptor 1; animal cell; Article; cell surface; controlled study; cytokine release; flow cytometry; gene knockdown; human; human cell; immunofluorescence; intracellular signaling; limit of quantitation; macrophage; male; New Zealand White (rabbit); nonhuman; polarization; protein expression; real time reverse transcription polymerase chain reaction; RNA interference; RNA isolation; THP-1 cell line; adverse event; animal; cell polarity; drug effect; Leporidae; lipid diet; macrophage; metabolism; physiology; signal transduction; Animals; Cell Polarity; Diet, High-Fat; Humans; Lipoproteins, LDL; Macrophages; Male; Rabbits; Scavenger Receptors, Class E; Signal Transduction; THP-1 Cellsjournal article10.1007/s10753-020-01229-6323942862-s2.0-85084442795WOS:000531748800001https://scholars.lib.ntu.edu.tw/handle/123456789/533866