Inhibitory effects of fluvastatin on activation of THP-1 cells induced by anti-beta2GPI/beta2GPI complex.
- Author:
Ting WANG
1
;
Hong ZHOU
1
;
Hong-Xiang XIE
1
;
Long-Fei XIA
1
;
Yuan MU
1
Author Information
1. School of Medical Science and Laboratory Medicine, Jiangsu University, Zhenjiang 212013, China.
- Publication Type:Journal Article
- MeSH:
Antigen-Antibody Complex;
pharmacology;
Cell Line;
Dose-Response Relationship, Drug;
Fatty Acids, Monounsaturated;
administration & dosage;
pharmacology;
Humans;
Hydroxymethylglutaryl-CoA Reductase Inhibitors;
administration & dosage;
pharmacology;
I-kappa B Proteins;
metabolism;
Indoles;
administration & dosage;
pharmacology;
Monocytes;
cytology;
metabolism;
NF-KappaB Inhibitor alpha;
Phosphorylation;
RNA, Messenger;
metabolism;
Signal Transduction;
drug effects;
Thromboplastin;
genetics;
metabolism;
Transcription Factor RelA;
metabolism;
Tumor Necrosis Factor-alpha;
genetics;
metabolism;
beta 2-Glycoprotein I;
antagonists & inhibitors;
immunology
- From:
Acta Pharmaceutica Sinica
2013;48(10):1550-1556
- CountryChina
- Language:Chinese
-
Abstract:
This study is to explore the interventional effects of fluvastatin on anti-beta2GPI/beta2GPI-induced activation in THP-1 mononuclear cells. In vitro, human mononuclear cells THP-1 were treated with fluvastatin, LPS and anti-beta2GPI/beta2GPI, then the TF expression on THP-1 cells was detected by real-time quantitative PCR (RT-qPCR) or TF activity was detected by kit. TNF-alpha mRNA and its protein expression were investigated by RT-PCR and ELISA kit. The expression of phospho-NF-kappaB p65 and inhibitory protein of NF-kappaB (IkappaB-alpha) were measured by Western blotting. The results suggested that the expression of TF and TNF-alpha on THP-1 cells was significantly up-regulated with treatment of anti-beta2GPI/beta2GPI complex (100 mg x L(-1)), compared with that of untreated cells (P < 0.05). Fluvastatin (50 mg x L(-1)) could decrease TF (mRNA and activity) expression and the level of TNF-alpha (mRNA and protein) in THP-1 cells with anti-beta2GPI/beta2GPI complex. The expression of TF and TNF-alpha was shown in a concentration-dependent manner. Moreover, anti-beta2GPI/beta2GPI complex could downregulate IkappaB-alpha levels and increase the levels of phospho-NF-kappaB p65. And these effects of anti-beta2GPI/beta2GPI complex could be blocked by fluvastatin. In conclusion, fluvastatin may interfere the expression and regulation of NF-kappaB signal transduction pathway, thereby inhibit the effects of anti-beta2GPI/beta2GPI on activation of THP-1 cells, by decreasing the expression of TF and TNF-alpha.
