Simvastatin suppress lipopolysaccharides induced upregulation of lipoprotein associated phospholipase A(2) expression in macrophages via inactivation of p38MAPK pathway.
- Author:
Wen-ying JIN
1
;
Jing-yi REN
;
Hong CHEN
Author Information
- Publication Type:Journal Article
- MeSH: 1-Alkyl-2-acetylglycerophosphocholine Esterase; Anthracenes; pharmacology; Butadienes; pharmacology; Cells, Cultured; Humans; Imidazoles; pharmacology; Lipopolysaccharides; pharmacology; Macrophages; drug effects; metabolism; Monocytes; drug effects; metabolism; Nitriles; pharmacology; Phospholipases A2; metabolism; Phosphorylation; Pyridines; pharmacology; RNA, Messenger; genetics; Simvastatin; pharmacology; p38 Mitogen-Activated Protein Kinases; metabolism
- From: Chinese Journal of Cardiology 2010;38(10):923-928
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVETo investigate the effects of simvastatin on lipopolysaccharides (LPS) induced upregulation of Lp-PLA(2) in human peripheral blood monocytes-macrophages and the related mechanisms.
METHODSPeripheral 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.
CONCLUSIONThis 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.
