Atorvastatin attenuates TLR4-mediated NF-κB activation in a MyD88-dependent pathway

Abstract

Antigen presenting cells such as dendritic cells and macrophages have recently been detected in atherosclerotic plaques. Toll-like receptors expressed on the surface of these cells, have been implicated in ongoing inflammatory responses in the plaques. In this study, we investigated the anti-inflammatory effect of atorvastatin, a lipid lowering drug, via Toll-like receptor 4 (TLR4) in vitro, employing murine pro-B cell lines transfected with hTLR4/MD2 and MyD88/hTLR4/MD2 systems. The results showed that atorvastatin at 10 μM significantly attenuated NF-κB activation within 24 hours while at lower doses of 0.1 and 1 μM, treatment time had to be prolonged up to 48 hours for a significant inhibition to occur. The inhibition of NF-κB was also observed in a cell line cotransfected with MyD88 and TLR4 suggesting that the attenuation of NF-κB by atorvastatin occurred in a MyD88 dependent fashion.