title: Atorvastatin decreases Toll-like receptor 4 expression and downstream signaling in human monocytic leukemia cells.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Cardiology, Central Hospital, Fengxian District, Shanghai 201400, China.
authors.forename: Shuan Suo
authors.initials: SS
authors.lastname: Yang
authors.forename: Ruogu
authors.initials: R
authors.lastname: Li
authors.forename: Xinkai
authors.initials: X
authors.lastname: Qu
authors.forename: Weiyi
authors.initials: W
authors.lastname: Fang
authors.forename: Zhe
authors.initials: Z
authors.lastname: Quan
mesh_terms: D000069059:Atorvastatin; D015153:Blotting, Western; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D015973:Gene Expression Regulation, Leukemic / Q000187:drug effects*; D006538:Heptanoic Acids / Q000494:pharmacology*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D007938:Leukemia / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism; D011758:Pyrroles / Q000494:pharmacology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects*; D051197:Toll-Like Receptor 4 / Q000235:genetics* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D053583:Interleukin-1beta; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D011758:Pyrroles; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D000069059:Atorvastatin