Chinese Journal of Tissue Engineering Research ›› 2011, Vol. 15 ›› Issue (20): 3701-3705.doi: 10.3969/j.issn.1673-8225.2011.20.022

Previous Articles     Next Articles

Atorvastatin intervention and peroxisome proliferator-activated receptor gamma expression in human primary monocytes

Xi Zi-zhong1, Yang Lei2, Wang Ye3, Wang Xiao-bin1, Zhang Hai-qi1   

  1. 1Liaoning Medical University, Jinzhou  121001, Liaoning Province, China
    2Zhangzhongjing Traditional Medical College, Nanyang Institute of Technology, Nanyang  473000, Henan Province, China
    3Department of Neurology, the General Hospital of Shenyang Military Command of Chinese PLA, Shenyang  110016, Liaoning Province, China
  • Received:2011-01-17 Revised:2011-02-19 Online:2011-05-14 Published:2011-05-14
  • Contact: Wang Ye, Doctor, Associate chief physician, Master’s supervisor, Department of Neurology, the General Hospital of Shenyang Military Command of Chinese PLA, Shenyang 110016, Liaoning Province, China Wangyedr@sina.com
  • About author:Xi Zi-zhong★, Studying for master’s degree, Physician, Liaoning Medical University, Jinzhou 121001, Liaoning Province, China Xizizhong06@yahoo.com.cn Wang Xiao-bin, Studying for master’s degree, Physician, Liaoning Medical University, Jinzhou 121001, Liaoning Province, China Zhang Hai-qi, Studying for master’s degree, Physician, Liaoning Medical University, Jinzhou 121001, Liaoning Province, China Xi Zi-zhong, Wang Xiao-bin, and Zhang Hai-qi contributed equally to this paper.

PDF

298

Abstract:

BACKGROUND: Peroxisome proliferator-activated receptor gamma (PPAR-γ) is known about its importance to the generation and development of ischemic diseases. A great amount of researches have proved that atorvastatin as PPAR-γ receptor agonist can not only adjust lipid metabolism, but also suppress inflammatory transmitter production. But the exact mechanism of anti-inflammatory action of atorvastatin still remains unknown.
OBJECTIVE: To investigate the anti-inflammatory effects of astorvastatin on PPAR-γ in primary human monocytes.
METHODS: Human peripheral monocytes which non-activated by tumor necrosis factor-alpha (TNF-α) were randomly divided into 5 groups. The first group was control group, second group was incubated with 10 µmol/L atorvastatin, third group were incubated with 1 µmol/L atorvastatin, fourth group was incubated with 0.1 µmol/L atorvastatin, fifth group was incubated with anti-PPAR-γ antibody; Human peripheral monocytes which stimulated by 1 μg/L TNF-αwere randomly divided into 4 groups. The first group was control group, second group was incubated with 0.1 µmol/L atorvastatin, third group was incubated with 1 µmol/L atorvastatin, fourth group was incubated with 10 µmol/L atorvastatin, and each group was incubated for up to 24 hours. Then PPAR-γ expression was analyzed by electrophoretic mobility shift assay. Pro-inflammatory cytokines, including TNF-α, monocyte chemoattractant protein-1 (MCP-1) and gelatinase B, were measured by enzyme-linked immunosorbent assays, and oxygen consumption was determined polarographically with a Clark-type oxygen electrode.
RESULTS AND CONCLUSION: We found that atorvastatin in monocytes non-stimulated by TNF-α in a dose-dependent manner activated PPAR-γ and lowered MCP-1 levels (P < 0.05) and gelatinase B (P < 0.05), but showed no influence on TNF-α. We also found in TNF-α-stimulated monocytes the PPAR-γ protein expression was suppressed and PPAR-γ activation in response to atorvastatin treatment was less pronounced, but atorvastatin still resulted in a dose-dependent decrease in TNF-a levels (P < 0.05) and MCP-1, and a reduction in matrix metalloproteinase 9. Moreover, atorvastatin shows dose-dependent inhibition of cellular oxygen consumption up to 41%. These indicated that atorvastatin exerts strictly anti-inflammatory effects, but the anti-inflammatory properties of atorvastatin are not completely dependent on PPAR-γ pathway.

CLC Number: