title: Artemisinin inhibits the proliferation, migration, and inflammatory reaction induced by tumor necrosis factor-α in vascular smooth muscle cells through nuclear factor kappa B pathway.
abstract: BACKGROUND
  Atherosclerosis is an inflammatory disease with the most common pathologic process leading to cardiovascular diseases. The aim of this study was to evaluate the effect of artemisinin (ART) on the proliferation, migration, and inflammation induced by tumor necrosis factor-α (TNF-α) of rat vascular smooth muscle cells (VSMCs).
  
  
  METHODS
  Primary rat VSMCs were pretreated with ART and then co-incubated with TNF-α. Cell proliferation was evaluated by MTT assay. Cell migration was assessed by transwell assay. Reactive oxygen species (ROS) production was measured by flow cytometry after staining with dichloro-dihydro-fluorescein diacetate. Inflammation factors of nitric oxide and prostaglandin E2 (PGE2) were measured by responding assay kits. Expression levels of nuclear factor kappa B (NF-κB) subunit NF-κB p65 and the regulator inhibitor of nuclear factor kappa-B kinase-alpha (IκBα) were tested by Western blot, meanwhile, the activation of NF-κB was observed by immunofluorescence assay.
  
  
  RESULTS
  The proliferation, migration, and inflammation of VSMCs induced by TNF-α were significantly inhibited by ART treatment in a dose-dependent manner. Treatment with 100 μM ART for 2 h significantly reduced the expression of proliferating cell nuclear antigen and migration-related proteins matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9). On the other hand, the same treatment decreased the inflammation factors production of nitric oxide and PGE2. Fluorescence-activated cell sorting analysis revealed that ART suppressed the ROS production induced by TNF-α. Western blot analysis showed that both inflammation mediators inducible nitric oxide synthase and cyclooxygenase and the NF-κB pathway subunit NF-κB p65 were downregulated by ART.
  
  
  CONCLUSIONS
  The results suggest that ART can effectively inhibit the proliferation, migration, and inflammation of VSMCs induced by TNF-α through ROS-mediated NF-κB signal pathway.
authors.affiliation: Department of Cardiology, Shengjing Hospital of China Medical University, Shenyang, People's Republic of China. Electronic address: caoqiancq@outlook.com.
authors.forename: Qian
authors.initials: Q
authors.lastname: Cao
authors.affiliation: Department of Emergency Medicine, Shengjing Hospital of China Medical University, Shenyang, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Cardiology, Shengjing Hospital of China Medical University, Shenyang, People's Republic of China.
authors.forename: Jin
authors.initials: J
authors.lastname: Shi
authors.affiliation: Department of Cardiology, Shengjing Hospital of China Medical University, Shenyang, People's Republic of China.
authors.forename: Changlu
authors.initials: C
authors.lastname: Xu
authors.affiliation: Department of Cardiology, Shengjing Hospital of China Medical University, Shenyang, People's Republic of China.
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Cardiology, Shengjing Hospital of China Medical University, Shenyang, People's Republic of China.
authors.forename: Tiangui
authors.initials: T
authors.lastname: Yang
authors.affiliation: Department of Cardiology, Shengjing Hospital of China Medical University, Shenyang, People's Republic of China.
authors.forename: Peng
authors.initials: P
authors.lastname: Fu
authors.affiliation: Department of Cardiology, Shengjing Hospital of China Medical University, Shenyang, People's Republic of China.
authors.forename: Tiesheng
authors.initials: T
authors.lastname: Niu
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001013:Aorta, Thoracic / Q000166:cytology; D019306:Artemisia; D037621:Artemisinins / Q000494:pharmacology / Q000627:therapeutic use*; D050197:Atherosclerosis / Q000517:prevention & control*; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D020672:I-kappa B Proteins / Q000378:metabolism; D007249:Inflammation / Q000188:drug therapy; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000166:cytology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha; D016328:NF-kappa B / Q000378:metabolism; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000890:Anti-Infective Agents; D037621:Artemisinins; D020672:I-kappa B Proteins; D016328:NF-kappa B; C000606206:Nfkbia protein, rat; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D014409:Tumor Necrosis Factor-alpha; D000072000:NF-KappaB Inhibitor alpha; C031327:artemisinin
keywords: Artemisinin; Cell proliferation; Migration and inflammation; TNF-α; Vascular smooth muscle cells (VSMCs)