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

Cell Immunol. 2012 Sep;279(1):96-102. doi: 10.1016/j.cellimm.2012.09.008. Epub 2012 Oct 1.

Abstract

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-κB protein, and expression of TNF-α, IL-6, and IL-1β in lipopolysaccharide-induced THP-1 cells after incubation with different concentrations of atorvastatin (0.1, 1, 10, 20μM) 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-κB expression, and levels of TNF-α, IL-6, and IL-1β 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.

MeSH terms

  • Atorvastatin
  • Blotting, Western
  • Cell Line, Tumor
  • Dose-Response Relationship, Drug
  • Enzyme-Linked Immunosorbent Assay
  • Flow Cytometry
  • Gene Expression Regulation, Leukemic / drug effects*
  • Heptanoic Acids / pharmacology*
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology
  • Interleukin-1beta / metabolism
  • Interleukin-6 / metabolism
  • Leukemia / genetics
  • Leukemia / metabolism
  • Leukemia / pathology
  • Lipopolysaccharides / pharmacology
  • Monocytes / drug effects
  • Monocytes / metabolism
  • Monocytes / pathology
  • NF-kappa B / metabolism
  • Pyrroles / pharmacology*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / drug effects*
  • Toll-Like Receptor 4 / genetics*
  • Toll-Like Receptor 4 / metabolism
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Heptanoic Acids
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Interleukin-1beta
  • Interleukin-6
  • Lipopolysaccharides
  • NF-kappa B
  • Pyrroles
  • TLR4 protein, human
  • Toll-Like Receptor 4
  • Tumor Necrosis Factor-alpha
  • Atorvastatin