title: C-reactive protein stimulates RAGE expression in human coronary artery endothelial cells in vitro via ROS generation and ERK/NF-κB activation.
abstract: OBJECTIVE
  The receptor for advanced glycation end-products (RAGE) plays an important role in development of atherosclerosis, and C-reactive protein (CRP) has been found to stimulate its expression in endothelial cells. In this study we investigated how CRP regulated the expression of RAGE in human coronary artery endothelial cells (HCAECs).
  
  
  METHODS
  HCAECs were treated in vitro with CRP (50 μg/mL) in combination with a variety of inhibitors. ROS generation was determined by immunocytochemistry and flow cytometry. The RAGE expression and phosphorylation of relevant signaling proteins were measured using Western blot analyses.
  
  
  RESULTS
  CRP stimulated the expression of RAGE in the cells, accompanied by markedly increased ROS generation, phosphorylation of ERK1/2 and NF-κB p65, as well as translocation of NF-κB p65 to the nuclei. CRP also stimulated phosphorylation of JNK and p38 MAPK. Pretreatment of the cells with the ROS scavenger N-acetyl-L-cysteine, ERK inhibitor PD98059 or NF-κB inhibitor PDTC blocked CRP-stimulated RAGE expression, but pretreatment with the NADPH oxidase inhibitor DPI, JNK inhibitor SP600125 or p38 MAPK inhibitor SB203580 did not significantly alter CRP-stimulated RAGE expression.
  
  
  CONCLUSIONS
  CRP stimulates RAGE expression in HCAECs in vitro via ROS generation and activation of the ERK/NF-κB signaling pathway.
authors.affiliation: Guangzhou Institute of Cardiovascular Disease, Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Zhong
authors.affiliation: Guangzhou Institute of Cardiovascular Disease, Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, China.
authors.forename: Chuan-fang
authors.initials: CF
authors.lastname: Cheng
authors.affiliation: Guangzhou Institute of Cardiovascular Disease, Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, China.
authors.forename: Yi-zhi
authors.initials: YZ
authors.lastname: Luo
authors.affiliation: Guangzhou Institute of Cardiovascular Disease, Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, China.
authors.forename: Chao-wei
authors.initials: CW
authors.lastname: Tian
authors.affiliation: Guangzhou Institute of Cardiovascular Disease, Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Yang
authors.affiliation: Guangzhou Institute of Cardiovascular Disease, Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, China.
authors.forename: Ben-rong
authors.initials: BR
authors.lastname: Liu
authors.affiliation: Guangzhou Institute of Cardiovascular Disease, Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, China.
authors.forename: Min-sheng
authors.initials: MS
authors.lastname: Chen
authors.affiliation: 1] Guangzhou Institute of Cardiovascular Disease, Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, China [2] Department of Pharmacology & Toxicology, Boonshoft School of Medicine, Wright State University, Dayton, OH 45324, USA.
authors.forename: Yan-fang
authors.initials: YF
authors.lastname: Chen
authors.affiliation: Guangzhou Institute of Cardiovascular Disease, Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, China.
authors.forename: Shi-ming
authors.initials: SM
authors.lastname: Liu
mesh_terms: D002097:C-Reactive Protein / Q000276:immunology*; D002478:Cells, Cultured; D003331:Coronary Vessels / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D042783:Endothelial Cells / Q000187:drug effects / Q000276:immunology*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D016328:NF-kappa B / Q000032:analysis / Q000037:antagonists & inhibitors / Q000276:immunology*; D017382:Reactive Oxygen Species / Q000276:immunology*; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000032:analysis / Q000276:immunology*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D016328:NF-kappa B; D017382:Reactive Oxygen Species; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D002097:C-Reactive Protein
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