title: Atorvastatin suppresses NLRP3 inflammasome activation via TLR4/MyD88/NF-κB signaling in PMA-stimulated THP-1 monocytes.
abstract: OBJECTIVE
  Increasing evidence shows that NLRP3 inflammasome is closely associated with the progression of atherosclerosis. The purpose of the present study was to evaluate the effects of atorvastatin on NLRP3 inflammasome in PMA-stimulated THP-1 cells and explore its underlying mechanism.
  
  
  METHODS
  Human monocytic THP-1 cells were pretreated with atorvastatin for 1h and then induced by PMA for 48h. Total protein was collected for real-time PCR and Western blot analysis. Cytokine IL-1β release was detected by ELISA assay. And the NF-κB p65 translocation was detected by cellular NF-κB translocation kit.
  
  
  RESULTS
  It was shown that atorvastatin significantly reduced the expression of NLRP3, the cleavage of caspase-1 and IL-1β in PMA-induced THP-1 cells. Moreover, Bay (a NF-κB inhibitor) treatment greatly suppressed the expression of NLRP3, the cleavage of caspase-1 and IL-1β in PMA-induced THP-1 cells, suggesting that the activation of NF-κB pathway takes part in regulating the expression of NLRP3 inflammasome. In addition, atorvastatin markedly inhibited the up-regulation of toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88) and the activation of nuclear factor kappa b (NF-κB) in PMA-stimulated THP-1 cells.
  
  
  CONCLUSIONS
  Atorvastatin exerts an anti-inflammatory effect by inhibiting NLRP3 inflammasome through suppressing TLR4/MyD88/NF-κB pathway in PMA-induced THP-1 monocytes.
authors.affiliation: Department of Cardiology, The Key Lab of Cardiovascular disease of Wenzhou, The First Affiliated Hospital of Wenzhou Medical University, 2 Fuxue Road, Wenzhou, Zhejiang 325000, PR China. Electronic address: 676888452@qq.com.
authors.forename: Fanqi
authors.initials: F
authors.lastname: Kong
authors.affiliation: Department of Cardiology, The Key Lab of Cardiovascular disease of Wenzhou, The First Affiliated Hospital of Wenzhou Medical University, 2 Fuxue Road, Wenzhou, Zhejiang 325000, PR China. Electronic address: fredye2012@163.com.
authors.forename: Bozhi
authors.initials: B
authors.lastname: Ye
authors.affiliation: Department of Cardiology, The Key Lab of Cardiovascular disease of Wenzhou, The First Affiliated Hospital of Wenzhou Medical University, 2 Fuxue Road, Wenzhou, Zhejiang 325000, PR China. Electronic address: 315601953@qq.com.
authors.forename: Lu
authors.initials: L
authors.lastname: Lin
authors.affiliation: Department of Cardiology, The Key Lab of Cardiovascular disease of Wenzhou, The First Affiliated Hospital of Wenzhou Medical University, 2 Fuxue Road, Wenzhou, Zhejiang 325000, PR China. Electronic address: cardiosherry@163.com.
authors.forename: Xueli
authors.initials: X
authors.lastname: Cai
authors.affiliation: Department of Cardiology, The Key Lab of Cardiovascular disease of Wenzhou, The First Affiliated Hospital of Wenzhou Medical University, 2 Fuxue Road, Wenzhou, Zhejiang 325000, PR China. Electronic address: weijianhuang69@126.com.
authors.forename: Weijian
authors.initials: W
authors.lastname: Huang
authors.affiliation: Department of Cardiology, The Key Lab of Cardiovascular disease of Wenzhou, The First Affiliated Hospital of Wenzhou Medical University, 2 Fuxue Road, Wenzhou, Zhejiang 325000, PR China. Electronic address: susiehzq@hotmail.com.
authors.forename: Zhouqing
authors.initials: Z
authors.lastname: Huang
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D000069059:Atorvastatin / Q000737:chemistry / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D058847:Inflammasomes / Q000378:metabolism*; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism*; D053594:Myeloid Differentiation Factor 88 / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
chemical_list: D058847:Inflammasomes; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C453881:NLRP3 protein, human; D051197:Toll-Like Receptor 4; D000069059:Atorvastatin; D013755:Tetradecanoylphorbol Acetate
keywords: Atherosclerosis; Atorvastatin; Monocytes; NLRP3 inflammasome; TLR4/MyD88/NF-κB