Simvastatin attenuates the lipopolysaccharideinduced inflammatory response of rat pulmonary microvascular endothelial cells by downregulating toll-like receptor 4 expression.
Cent Eur J Med
; 9(1): 133-140, 2014.
Article
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| MEDLINE
| ID: mdl-32288932
ABSTRACT
OBJECTIVE:
The therapeutic potential of simvastatin as an anti-inflammatory agent was explored by investigating its effect on the lipopolysaccharide (LPS)-induced inflammatory response in rat pulmonary microvascular endothelial cells (RPMVECs).METHODS:
RPMVECs were isolated and the mRNA and protein levels of different toll-like receptors (TLR) were assessed by qRT-PCR and western blotting. The LPS-induced expressions of TLR4, TNF-α and iNOS were analyzed in RPMVECs treated with different concentrations of simvastatin for different times. NF-κB activation was examined by immuofluroscence, luciferase reporter assay and western blotting.RESULTS:
TLR4 is abundantly expressed in RPMVECs, and its expression is induced by LPS stimulation. Simvastatin inhibited LPS-induced TLR4 expression at the mRNA and protein levels in a time-dependent manner (p<0.01), and alleviated inflammation in RPMVECs by inhibiting the release of inflammatory factors such as TNF-α and iNOS. Further study indicated that simvastatin significantly attenuated NF-κB activity by inhibiting the degradation of IκB-α. Pretreatment with pyrrolidine dithiocarbamate (PDTC) and knock-down of TLR4 expression by RNA interference down-regulated the LPS-induced inflammatory response in RPMVECs.CONCLUSION:
Simvastatin inhibits the LPS-induced inflammatory response in RPMVECs by down-regulating TLR4 expression, suggesting its role as a potential inhibitor of LPS-induced inflammation.
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Cent Eur J Med
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2014
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Article