title: Curcumin inhibits LPS-induced inflammation in rat vascular smooth muscle cells in vitro via ROS-relative TLR4-MAPK/NF-κB pathways.
abstract: OBJECTIVE
  To investigate whether curcumin (Cur) suppressed lipopolysaccharide (LPS)-induced inflammation in vascular smooth muscle cells (VSMCs) of rats, and to determine its molecular mechanisms.
  
  
  METHODS
  Primary rat VSMCs were treated with LPS (1 μg/L) and Cur (5, 10, or 30 μmol/L) for 24 h. The levels of MCP-1, TNF-α, and iNOS were measured using ELISA and real-time RT-PCR. NO level was analyzed with the Griess reaction. Western-blotting was used to detect the activation of TLR4, MAPKs, IκBα, NF-κB p65, and the p47(phox) subunit of NADPH oxidase in the cells.
  
  
  RESULTS
  Treatment of VSMCs with LPS dramatically increased expression of inflammatory cytokines MCP-1 and TNF-α, expression of TLR4 and iNOS, and NO production. LPS also significantly increased phosphorylation of IκBα, nuclear translocation of NF-κB (p65) and phosphorylation of MAPKs in VSMCs. Furthermore, LPS significantly increased production of intracellular ROS, and decreased expression of p47(phox) subunit of NADPH oxidase. Pretreatment with Cur concentration-dependently attenuated all the aberrant changes in LPS-treated VSMCs. The LPS-induced overexpression of MCP-1 and TNF-α, and NO production were attenuated by pretreatment with the ERK inhibitor PD98059, the p38 MAPK inhibitor SB203580, the NF-κB inhibitor PDTC or anti-TLR4 antibody, but not with the JNK inhibitor SP600125.
  
  
  CONCLUSIONS
  Cur suppresses LPS-induced overexpression of inflammatory mediators in VSMCs in vitro via inhibiting the TLR4-MAPK/NF-κB pathways, partly due to block of NADPH-mediated intracellular ROS production.
authors: Department of Cardiology, The Second Affiliated Hospital, Xi'-an Jiaotong University School of Medicine, Xi-an, China.
authors: Zhe
authors: Z
authors: Meng
authors: Chao
authors: C
authors: Yan
authors: Qian
authors: Q
authors: Deng
authors: Deng-feng
authors: DF
authors: Gao
authors: Xiao-lin
authors: XL
authors: Niu
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003474:Curcumin / Q000494:pharmacology*; D007249:Inflammation / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors* / Q000737:chemistry; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000737:chemistry / Q000276:immunology / Q000378:metabolism*; D016328:NF-kappa B / Q000737:chemistry / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000737:chemistry / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000502:physiology*
chemical_list: D008070:Lipopolysaccharides; D016328:NF-kappa B; D017382:Reactive Oxygen Species; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; D003474:Curcumin
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