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Int J Clin Exp Pathol 2013;6(10):2129-2136

Original Article
MAPK/ERK signal pathway involved expression of COX-2 and VEGF by IL-1β induced in
human endometriosis stromal cells in vitro

Fengying Huang, Jing Cao, Qiuhong Liu, Ying Zou, Hongyun Li, Tuanfang Yin

Department of Obstetrics and Gynecology, Department of Otorhinolaryngology, The Second Xiangya Hospital, Central South University,
Changsha, Hunan, China, 410011

Received June 23, 2013; Accepted August 1, 2013; Epub September 15, 2013; Published October 1, 2013

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. (IJCEP1306023).

Keywords: Endometriosis stromal cells (ESC), cyclooxygenase-2 (COX-2), vascular endothelial growth factor (VEGF), cytokines, signal
pathways, in vitro

Address correspondence to: Dr. Tuanfang Yin, Department of Otorhinolaryngology, The Second Xiangya Hospital, Central South University,
Changsha, Hunan, China, 410011. Tel: +8613874870794; E-mail: Ytfyin@163.com