title: TLR4/NF-κB signaling pathway-mediated and oxLDL-induced up-regulation of LOX-1, MCP-1, and VCAM-1 expressions in human umbilical vein endothelial cells.
abstract: This study aimed to investigate the function and signaling pathway of Toll-like receptor 4 (TLR4) in oxidized low-density lipoprotein (oxLDL)-induced up-regulated expressions of oxidized LDL receptor 1 (LOX-1), monocyte chemoattractant protein 1 (MCP-1), and vascular cell adhesion molecule 1 (VCAM-1) in human umbilical vein endothelial cells (HUVECs). HUVECs were incubated with different oxLDL concentrations (0, 20, 40, 60, and 80 μg/mL) for 24 and 48 h. The influence of oxLDL on TLR4, LOX-1, MCP-1, and VCAM-1 expressions in HUVECs was detected by real-time polymerase chain reaction and Western blot analysis. HUVECs were transfected with small interfering RNA targeting TLR4 (siTLR4), in which protein expressions of LOX-1, MCP-1, and VCAM-1, and the nuclear translocation of NF-kB (P50) were detected by Western blot. After 48 h of processing HUVECs with pyrrolidine dithiocarbamate (PDTC), protein expressions of TLR4, LOX-1, MCP-1, and VCAM- 1 were detected by Western blot. OxLDL induced a concentration-dependent up-regulation of mRNA and protein expressions of TLR4, LOX-1, MCP-1, and VCAM-1 in HUVECs (P < 0.001). siTLR4 significantly reduced protein expressions of LOX-1, MCP-1, VCAM-1, and reduced the NF-kB (P50) nuclear translocation (P < 0.001). PDTC significantly inhibited protein expressions of TLR4, LOX-1, MCP- 1, and VCAM-1 (P < 0.001). Results of this study demonstrate that the TLR4/NF-κB signaling pathway has an important function in the up-regulation of oxLDL-induced expressions of LOX-1, MCP-1, and VCAM-1 in HUVECs.
authors.affiliation: Department of Cardiothoracic Surgery, The First Affiliated Hospital of the University of South China, Hengyang, Hunan Province, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Feng
authors.affiliation: Division of Cardiology, Shanghai Pudong Hospital, Fudan University, Pudong Medical Center, Shanghai, China.
authors.forename: Z R
authors.initials: ZR
authors.lastname: Cai
authors.affiliation: Institute of Cardiovascular Disease, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang, Hunan Province, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Tang
authors.affiliation: Institute of Cardiovascular Disease, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang, Hunan Province, China.
authors.forename: G
authors.initials: G
authors.lastname: Hu
authors.affiliation: Institute of Cardiovascular Disease, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang, Hunan Province, China.
authors.forename: J
authors.initials: J
authors.lastname: Lu
authors.affiliation: Institute of Cardiovascular Disease, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang, Hunan Province, China.
authors.forename: D
authors.initials: D
authors.lastname: He
authors.affiliation: Institute of Cardiovascular Disease, Key Laboratory for Atherosclerology of Hunan Province, University of South China, Hengyang, Hunan Province, China shuangwangcn@yeah.net.
authors.forename: S
authors.initials: S
authors.lastname: Wang
mesh_terms: D002448:Cell Adhesion / Q000235:genetics; D018932:Chemokine CCL2 / Q000096:biosynthesis* / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008077:Lipoproteins, LDL / Q000235:genetics* / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D051127:Scavenger Receptors, Class E / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction; D051197:Toll-Like Receptor 4 / Q000235:genetics*; D019010:Vascular Cell Adhesion Molecule-1 / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C111835:CCL2 protein, human; D018932:Chemokine CCL2; D008077:Lipoproteins, LDL; D016328:NF-kappa B; C495137:OLR1 protein, human; D051127:Scavenger Receptors, Class E; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D019010:Vascular Cell Adhesion Molecule-1; C099252:oxidized low density lipoprotein