title: Atorvastatin Attenuates TNF-alpha Production via Heme Oxygenase-1 Pathway in LPS-stimulated RAW264.7 Macrophages.
abstract: OBJECTIVE
  To assess the effect of atorvastatin on lipopolysaccharide (LPS)-induced TNF-α production in RAW264.7 macrophages.
  
  
  METHODS
  RAW264.7 macrophages were treated in different LPS concentrations or at different time points with or without atorvastatin. TNF-α level in supernatant was measured. Expressions of TNF-α mRNA and protein and heme oxygenase-1 (HO-1) were detected by ELISA, PCR, and Western blot, respectively. HO activity was assayed.
  
  
  RESULTS
  LPS significantly increased the TNF-α expression and secretion in a dose- and time-dependent manner. The HO-1 activity and HO-1 expression level were significantly higher after atorvastatin treatment than before atorvastatin treatment and attenuated by SB203580 and PD98059 but not by SP600125, suggesting that the ERK and p38 mitogen-activated protein kinase (MAPK) pathways participate in regulating the above-mentioned effects of atorvastatin. Moreover, the HO-1 activity suppressed by SnPP or the HO-1 expression inhibited by siRNA significantly attenuated the effect of atorvastatin on TNF-α expression and production in LPS-stimulated macrophages.
  
  
  CONCLUSIONS
  Atorvastatin can attenuate LPS-induced TNF-α expression and production by activating HO-1 via the ERK and p38 MAPK pathways, suggesting that atorvastatin can be used in treatment of inflammatory diseases such as sepsis, especially in those with atherosclerotic diseases.
authors.affiliation: Department of Anesthesiology, Nanfang Hospital of Southern Medical University, Guangzhou 510515, Guangdong, China; Department of Anesthesiology, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou 510260, Guangdong, China.
authors.forename: Xiao Qiao
authors.initials: XQ
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Guangzhou 510120, Guangdong, China; Guangdong Provincial Key Laboratory of Arrhythmia and Electrophysiology, Guangzhou 510120, Guangdong, China.
authors.forename: Nian Sang
authors.initials: NS
authors.lastname: Luo
authors.affiliation: Department of Surgery Intensive Care Unit, Nanfang Hospital of Southern Medical University, Guangzhou 510515, Guangdong, China.
authors.forename: Zhong Qing Chen
authors.initials: ZQ
authors.lastname: Salah
authors.affiliation: Department of Cardiology, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Guangzhou 510120, Guangdong, China; Guangdong Provincial Key Laboratory of Arrhythmia and Electrophysiology, Guangzhou 510120, Guangdong, China.
authors.forename: Yong Qing
authors.initials: YQ
authors.lastname: Lin
authors.affiliation: Department of Anesthesiology, Nanfang Hospital of Southern Medical University, Guangzhou 510515, Guangdong, China.
authors.forename: Miao Ning
authors.initials: MN
authors.lastname: Gu
authors.affiliation: Department of Cardiology, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University, Guangzhou 510120, Guangdong, China; Guangdong Provincial Key Laboratory of Arrhythmia and Electrophysiology, Guangzhou 510120, Guangdong, China.
authors.forename: Yang Xin
authors.initials: YX
authors.lastname: Chen
mesh_terms: D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D000069059:Atorvastatin; D004789:Enzyme Activation / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000235:genetics* / Q000378:metabolism; D006538:Heptanoic Acids / Q000494:pharmacology*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects*; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D011758:Pyrroles / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
chemical_list: D000276:Adjuvants, Immunologic; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D011758:Pyrroles; D014409:Tumor Necrosis Factor-alpha; D000069059:Atorvastatin; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse
keywords: Atorvastatin; Heme oxygenase-1; Lipopolysaccharide; Tumor necrosis factor-α