title: [Simvastatin suppress lipopolysaccharides induced upregulation of lipoprotein associated phospholipase A(2) expression in macrophages via inactivation of p38MAPK pathway].
abstract: OBJECTIVE
  To investigate the effects of simvastatin on lipopolysaccharides (LPS) induced upregulation of Lp-PLA(2) in human peripheral blood monocytes-macrophages and the related mechanisms.
  
  
  METHODS
  Peripheral blood monocytes of healthy volunteer were isolated and incubated for 2-3 days. Monocytes were incubated with various concentrations of LPS for 6 h or with 1 µg/ml of LPS for different times in LPS group. In simvastatin group and MAPK inhibitors groups, cells were pre-treated with simvastatin (10(-2) - 10(-7) mmol/L) or various MAPK inhibitors (10 µmol/L SB203580, 20 µmol/L U0126, and 20 µmol/L SP600125) before LPS co-incubation. Lp-PLA(2) activity was measured by chronometry, Lp-PLA(2) mRNA expression was detected by RT-PCR. Protein expressions of Lp-PLA(2) and p38MAPK and phosphorylated p38MAPK were examined by Western blot.
  
  
  RESULTS
  (1) LPS significantly upregulated Lp-PLA(2) mRNA and protein expression, as well as the enzyme activity in a time and concentration dependent manner, which could be significantly attenuated by simvastatin in a time and concentration dependent manner. (2) Simvastatin significantly reduced LPS-induced p38MAPK phosphorylation. The p38 MAPK inhibitor SB203580, but not MEK1/2 inhibitor U0126 and JNK inhibitor SP600125, completely prevented LPS-mediated up-regulation of Lp-PLA(2) at protein level.
  
  
  CONCLUSIONS
  This study demonstrated that LPS significantly upregulated Lp-PLA(2) mRNA and protein expression, as well as the enzyme activity in a time and concentration dependent manner via Rho-p38MAPK pathway, which could be significantly suppressed by simvastatin.
authors.affiliation: Department of Cardiology, Peking University People's Hospital, Beijing 100044, China.
authors.forename: Wen-ying
authors.initials: WY
authors.lastname: Jin
authors.forename: Jing-yi
authors.initials: JY
authors.lastname: Ren
authors.forename: Hong
authors.initials: H
authors.lastname: Chen
mesh_terms: D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D000873:Anthracenes / Q000494:pharmacology; D002070:Butadienes / Q000494:pharmacology; D002478:Cells, Cultured; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism*; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology; D054467:Phospholipases A2 / Q000378:metabolism*; D010766:Phosphorylation; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics; D019821:Simvastatin / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000873:Anthracenes; D002070:Butadienes; D007093:Imidazoles; D008070:Lipopolysaccharides; D009570:Nitriles; D011725:Pyridines; D012333:RNA, Messenger; C113580:U 0126; C432165:pyrazolanthrone; D019821:Simvastatin; D048051:p38 Mitogen-Activated Protein Kinases; D054467:Phospholipases A2; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; C526684:PLA2G7 protein, human; C093642:SB 203580