title: Tanshinone II A Attenuates TNF-α-Induced Expression of VCAM-1 and ICAM-1 in Endothelial Progenitor Cells by Blocking Activation of NF-κB.
abstract: OBJECTIVE
  Tanshinone IIA (Tan IIA) is effective in the treatment of inflammation and atherosclerosis. The adhesion of inflammatory cells to vascular endothelium plays important role in atherogenic processes. This study examined the effects of Tan IIA on expression of adhesion molecules in tumor necrosis factor-α (TNF-α)-induced endothelial progenitor cells (EPCs).
  
  
  METHODS
  EPCs were pretreated with Tan IIA and stimulated with TNF-α. Mononuclear cell (MNC) adhesion assay was performed to assess the effects of Tan IIA on TNF-α-induced MNC adhesion. Expression of vascular cell adhesion molecule-1 (VCAM-1)/intracellular adhesion molecule-1 (ICAM-1) and activation of Nuclear factor κB (NF-κB) signaling pathway were measured.
  
  
  RESULTS
  The results showed that the adhesion of MNCs to TNF-α-induced EPCs and expression of VCAM-1/ICAM-1 in EPCs were promoted by TNF-α, which were reduced by Tan IIA. TNF-α increased the amount of phosphorylation of NF-κB, IκB-α and IKKα/β in cytosolic fractions and NF-κB p65 in nucleus, while Tan IIA reduced its amount.
  
  
  CONCLUSIONS
  This study demonstrated a novel mechanism for the anti-inflammatory/anti-atherosclerotic activity of Tan IIA, which may involve down-regulation of VCAM-1 and ICAM-1 through partial blockage of TNF-α-induced NF-κB activation and IκB-α phosphorylation by the inhibition of IKKα/β pathway in EPCs.
authors.affiliation: Department of Cardiology, the First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, P.R. China.
authors.forename: Jin-Xiu
authors.initials: JX
authors.lastname: Yang
authors.forename: Yan-Yun
authors.initials: YY
authors.lastname: Pan
authors.forename: Jun-Hua
authors.initials: JH
authors.lastname: Ge
authors.forename: Bin
authors.initials: B
authors.lastname: Chen
authors.forename: Wei
authors.initials: W
authors.lastname: Mao
authors.forename: Yuan-Gang
authors.initials: YG
authors.lastname: Qiu
authors.forename: Xing-Xiang
authors.initials: XX
authors.lastname: Wang
mesh_terms: D045784:Abietanes / Q000494:pharmacology*; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D002448:Cell Adhesion / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D066026:Endothelial Progenitor Cells / Q000187:drug effects / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D020672:I-kappa B Proteins / Q000378:metabolism; D016130:Immunophenotyping; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism*; D008297:Male; D016328:NF-kappa B / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D051996:Transcription Factor RelA / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*
chemical_list: D045784:Abietanes; D020672:I-kappa B Proteins; D016328:NF-kappa B; D051996:Transcription Factor RelA; D014409:Tumor Necrosis Factor-alpha; D019010:Vascular Cell Adhesion Molecule-1; C021751:tanshinone; D018799:Intercellular Adhesion Molecule-1