Simvastatin suppress lipopolysaccharides induced upregulation of lipoprotein associated phospholipase A2 expression in macrohages via inactivation of p38MAPK pathway
10.3760/cma.j.issn.0253-3758.2010.10.013
- VernacularTitle:辛伐他汀抑制人外周血单核巨噬细胞脂蛋白相关磷脂酶A2表达
- Author:
Wen-Ying JIN
1
;
Jing-Yi REN
;
Hong CHEN
Author Information
1. 北京大学人民医院
- Keywords:
Atherosclerosis;
Mitogen-activated protein kinases;
Lipoprotein associated phospholipase A2;
Simvastatin
- From:
Chinese Journal of Cardiology
2010;38(10):923-928
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effects of simvastatin on lipopolysaccharides (LPS)induced upregulation of Lp-PLA2 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 - 10-7mmol/L)or various MAPK inhibitors ( 10 μmol/L SB203580, 20 μmol/L U0126,and 20 μmol/L SP600125) before LPS co-incubation. Lp-PLA2 activity was measured by chromometry, LpPLA2 mRNA expression was detected by RT-PCR. Protein expressions of Lp-PLA2 and p38MAPK and phosphorylated p38MAPK were examined by Western blot. Results ( 1 ) LPS significantly upregulated LpPLA2 mRNA and protein expression, as well as the enzyme activity in a time and concentration dependentmanner, 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-PLA2 at protein level. Conclusion This study demonstrated that LPS significantly upregulated Lp-PLA2 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.
