title: Constitutive and tumor necrosis factor-α-induced activation of nuclear factor-κB in adenomyosis and its inhibition by andrographolide.
abstract: OBJECTIVE
  To investigate the action of nuclear factor (NF)-κB in adenomyosis and evaluate the potential therapeutic effect of andrographolide on tumor necrosis factor (TNF)-α-induced expression of NF-κB-mediated genes cyclooxygease-2 (COX-2), vascular endothelial growth factor (VEGF), and tissue factor (TF) in adenomyotic stromal cells.
  
  
  METHODS
  Laboratory study using human tissues.
  
  
  METHODS
  Academic hospital.
  
  
  METHODS
  Twenty-nine patients (cases) with histologically confirmed adenomyosis and 14 (controls) without adenomyosis or endometriosis.
  
  
  METHODS
  Endometrial stromal cells derived from tissue samples harvested from both cases and controls were subjected to electrophoretic mobility shift assay, and gene and protein expression analyses.
  
  
  METHODS
  The NF-κB DNA-binding activity and protein levels of NF-κB subunits p50 and p65 and the messenger RNA (mRNA) and protein levels of NF-κB-mediated genes COX-2, VEGF, and TF in cases and controls, and their changes after stimulation with TNF-α and treatment with andrographolide.
  
  
  RESULTS
  The constitutive NF-κB DNA-binding activity and protein expression levels of p50 and p65, and mRNA and protein levels of COX-2, VEGF, and TF in cases were significantly higher than that of controls. The binding activity level correlated positively with dysmenorrhea severity in cases. The TNF-α stimulation further increased the binding activity, and the mRNA and protein levels of COX-2, VEGF, and TF, but treatment with andrographolide significantly reduced them.
  
  
  CONCLUSIONS
  NF-κB may be a pivotal transcription factor involved in the development of adenomyosis. Targeting NF-κB with inhibitors, like andrographolide, may hold promises of treating adenomyosis.
authors.affiliation: Shanghai Obstetrics and Gynecology Hospital, Fudan University, Shanghai, People's Republic of China.
authors.forename: Bin
authors.initials: B
authors.lastname: Li
authors.forename: Ming
authors.initials: M
authors.lastname: Chen
authors.forename: Xishi
authors.initials: X
authors.lastname: Liu
authors.forename: Sun-Wei
authors.initials: SW
authors.lastname: Guo
mesh_terms: D062788:Adenomyosis / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D016022:Case-Control Studies; D051546:Cyclooxygenase 2 / Q000235:genetics / Q000378:metabolism; D004224:Diterpenes / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D006801:Humans; D008875:Middle Aged; D016328:NF-kappa B / Q000235:genetics* / Q000378:metabolism; D013925:Thromboplastin / Q000235:genetics / Q000378:metabolism; D015533:Transcriptional Activation / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D004224:Diterpenes; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C030419:andrographolide; D013925:Thromboplastin; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human
keywords: Adenomyosis; COX-2; NF-κB; VEGF; andrographolide; constitutive activation; dysmenorrhea; severity; tissue factor