Atorvastatin decreases Toll-like receptor 4 expression and downstream signaling in human monocytic leukemia cells

Purpose: We aim to evaluate the effects of atorvastatin on the expression of Toll-like receptor (TLR4) protein and mRNA, and to explore their effects on TLR4-dependent downstream signaling in human monocytic leukemia (THP-1) cells. Methods: TLR4 protein and mRNA expression, levels of NF-kappa B protein, and expression of TNF-alpha, IL-6, and IL-1 beta in lipopolysaccharide-induced THP-1 cells after incubation with different concentrations of atorvastatin (0.1, 1, 10,20 mu M) were quantified via flow-cytometry, quantitative RT-PCR, western blotting, and ELSIA kits. Results: Atorvastatin incubation resulted in significant decreases in the levels of TLR4 protein and mRNA, NF-kappa B expression, and levels of TNF-alpha, IL-6, and IL-1 beta in LPS-induced THP-1 cells (P < 0.01). However, compared with the untreated control, the expression of these were significantly increased (P < 0.01). Conclusions: Atorvastatin could inhibit the TLR4 expression and TLR4-dependent downstream signaling in THP-1 cells. These observations imply that the interactions with innate immunity may serve as one of the pleiotropic mechanisms of atorvastatin. (C) 2012 Elsevier Inc. All rights reserved.