title: Oxidized low-density lipoprotein promotes macrophage lipid accumulation via the toll-like receptor 4-Src pathway.
abstract: BACKGROUND
  Uptake of oxidized low-density lipoprotein (oxLDL) by macrophages is recognized as a crucial step in the development of atherosclerosis, whereas the precise molecular mechanisms involving it remain to be elucidated.
  
  
  RESULTS
  This study focused on determining the role of toll-like receptor 4 (TLR4) and Src kinase in macrophage lipid accumulation. oxLDL significantly enhanced Src kinase activity and intracellular lipid contents in RAW264.7 macrophages, whereas the small interference RNA-mediated knockdown of TLR4 and Src or chemical inhibition of Src activity blocked oxLDL-induced lipid accumulation. Immunoprecipitation and immunofluorescence studies demonstrated that TLR4 was associated with Src on the plasma membrane upon oxLDL stimulation.
  
  
  CONCLUSIONS
  The results of the present study suggest an essential role of TLR4-Src signaling in macrophages in the pathogenesis of atherosclerosis.
authors.affiliation: Institute of Cardiovascular Disease, Ruijin Hospital, Jiaotong University School of Medicine.
authors.forename: Ke
authors.initials: K
authors.lastname: Yang
authors.forename: Xiaoqun
authors.initials: X
authors.lastname: Wang
authors.forename: Zhuhui
authors.initials: Z
authors.lastname: Liu
authors.forename: Lin
authors.initials: L
authors.lastname: Lu
authors.forename: Jinyan
authors.initials: J
authors.lastname: Mao
authors.forename: Hua
authors.initials: H
authors.lastname: Meng
authors.forename: Yanan
authors.initials: Y
authors.lastname: Wang
authors.forename: Yong
authors.initials: Y
authors.lastname: Hu
authors.forename: Ying
authors.initials: Y
authors.lastname: Zeng
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Zhang
authors.forename: Qiujing
authors.initials: Q
authors.lastname: Chen
authors.forename: Yan
authors.initials: Y
authors.lastname: Liu
authors.forename: Weifeng
authors.initials: W
authors.lastname: Shen
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000201:enzymology* / Q000235:genetics; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology; D002784:Cholesterol / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008077:Lipoproteins, LDL / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D051379:Mice; D008875:Middle Aged; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D000067996:RAW 264.7 Cells; D034622:RNA Interference; D015398:Signal Transduction / Q000187:drug effects; D013997:Time Factors; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D019061:src-Family Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D008077:Lipoproteins, LDL; D047428:Protein Kinase Inhibitors; C495345:TLR4 protein, human; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; C099252:oxidized low density lipoprotein; D002784:Cholesterol; D019061:src-Family Kinases