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Basic science: Cardiovascular disease basic research
e0110 The effects of atorvastatin on C-reactive protein induced Toll-like receptor 4 expression on CD14+ monocyte
  1. Jinlai Liu,
  2. Long Peng,
  3. Yanting Luo
  1. Department of Cardiology, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou, China

Abstract

Objective To observe the effects of atorvastatin on C-reactive protein (CRP) induced Toll-like receptor 4 expression on CD14+ monocyte in human, and anti-inflammatory effect of atorvastatin.

Methods CD14+ monocytes were isolated from blood in healthy volunteers by the Ficoll density gradient and stimulated by CRP with different concentrations (5, 25, 50, 100 μg/ml) and different exposure time (50 μg/ml CRP coincubated for 6, 12, 24 and 48 h). The protein expression of TLR4 was measured by flow cytometry and mRNA expression of TLR4 and MD-2 were tested by quantitative PCR. Measurements of TNFα, IL-6 and MMP-9 in the supernatants of cultured monocytes were performed by ELISA.

Results CRP (5, 25, 50 and 100 μg/ml) increased dose-dependently the expression of TLR4 protein (32.22±2.80%, 49.94±5.58%, 74.82±3.24% and 90.82±2.88%; p<0.005 vs control, respectively). CRP 50 μg/ml stimulated CD14+ monocytes for various times (6, 12, 24 and 48 h) and also increased time-dependently the expression of TLR4 protein (29.80±2.70%, 47.44±4.41%, 81.71±2.92% and 50.57±3.34%; p<0.005 vs control, respectively). Atorvastatin (1.0, 2.5, 5.0, 7.5 and 10 μmol/l) inhibited dose-dependently the expression of TLR4 protein induced by CRP 50 μg/ml for 24 h [68.17%, 52.43%, 27.72%, 17.46% and 9.99%; p<0.005 vs control (80.39%), respectively], and restrained dose-dependently the expression of TLR4 mRNA (p<0.005 vs control, respectively) and MD2 mRNA (p<0.005 vs control, respectively). The release of TNFα, IL-6 and MMP-9 in the supernatants of monocytes treated with CRP 50 μg/ml was inhibited dose-dependently by atorvastatin. Atorvastatin 10 μmol/l inhibited mostly the release of TNFα, IL-6 and MMP-9 in the supernatants of monocytes treated with CRP 50 μg/ml (24%, 22.6% and 15.6%, p<0.005 vs baseline, respectively).

Conclusion CRP can increase dose-dependently and time-dependently the expression of TLR4 on CD14+ monocyte in human, and the production of TNFα, IL-6 and MMP-9 in CD14+ monocyte. Atorvastatin can inhibit dose-dependently the expression of TLR4 mRNA and protein induced by CRP and the release of TNFα, IL-6 and MMP-9 in CD14+ monocytes in human. Atorvastatin has anti-inflammatory effects and may restrain innate immune response in vitro by inhibition of monocyte Toll-like receptor signalling.

  • Atorvastatin
  • toll-like receptor 4
  • C-reactive protein
  • monocyte
  • inflammation

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