title: MAPK/ERK signal pathway involved expression of COX-2 and VEGF by IL-1β induced in human endometriosis stromal cells in vitro.
abstract: OBJECTIVE
  Now there are more and more evidences that Cyclooxygenase-2 (COX-2) plays an important role in angiogenesis of endometriosis (EMs). Vascular endothelial growth factor (VEGF) has a potent angiogenic activity. However, it is worth studying about the regulating mechanism of COX-2/COX-1 and VEGF in the development of human endometriosis in vitro. The current study was designed to investigate the effect of 4 cytokines on COX-2/COX-1 expression and the effect of IL-1β on VEGF release in human endometriosis stromal cells (ESC), and to explore the related signaling pathways involved in vitro.
  
  
  METHODS
  Isolation, culture and identification of ESC. Cells were treated with 4 cytokines, and the inhibitor mitogen-activated protein-Erk (MEK) and the inhibitor p38 mitogen-activated protein kinase (MAPK) prior to adding cytokine IL-1β. COX-2 protein expression was measured by western blot and VEGF secretion was determined by ELISA.
  
  
  RESULTS
  Among four kinds of cytokines, IL-1β treatment increased COX-2 protein expression and VEGF release in three ESC, and TNF-α had the same effect on COX-2 protein level as IL-1β only in ectopic and eutopic ESC, and MCSF had only slight effect on ectopic ESC. In contrast, cytokines had no effect on COX-1 expression. We also demonstrated that MAPK reduced the synthesis of COX-2 by IL-1β induced. COX-2 inhibitor reduced VEGF release by IL-1β induced.
  
  
  CONCLUSIONS
  i) In human ESC in vitro, IL-1β up-regulated the COX-2 expression through the activation of p38 MAPK pathway, and not to COX-1. ii) Up-regulation of VEGF level by IL-1β treatment was found in human endometriosis stromal cell and COX-2 inhibitor was involved in this process.
authors.affiliation: Department of Obstetrics and Gynecology, The Second Xiangya Hospital, Central South University Changsha, Hunan, China, 410011.
authors.forename: Fengying
authors.initials: F
authors.lastname: Huang
authors.forename: Jing
authors.initials: J
authors.lastname: Cao
authors.forename: Qiuhong
authors.initials: Q
authors.lastname: Liu
authors.forename: Ying
authors.initials: Y
authors.lastname: Zou
authors.forename: Hongyun
authors.initials: H
authors.lastname: Li
authors.forename: Tuanfang
authors.initials: T
authors.lastname: Yin
mesh_terms: D000328:Adult; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D004715:Endometriosis / Q000378:metabolism* / Q000473:pathology; D004717:Endometrium / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D053583:Interleukin-1beta / Q000494:pharmacology*; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D016173:Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D017154:Stromal Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D042461:Vascular Endothelial Growth Factor A; D016173:Macrophage Colony-Stimulating Factor; D007371:Interferon-gamma; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human
keywords: Endometriosis stromal cells (ESC); cyclooxygenase-2 (COX-2); cytokines; in vitro; signal pathways; vascular endothelial growth factor (VEGF)