Endometriosis Research Today is a free monthly online journal that collates and summarizes the latest research about Endometriosis, including details on causes, treatment, symptoms, infertility. | ||||||||
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Distinct regulation of cyclooxygenase-2 by interleukin-1beta in normal and endometriotic stromal cells.Wu MH, Wang CA, Lin CC, Chen LC, Chang WC, Tsai SJ The Institute of Clinical Medicine, Department of Obstetrics and Gynecology, College of Medicine, National Cheng Kung University, 1 University Road, Tainan 70101, Taiwan, Republic of China. Aberrant production of cyclooxygenase-2 (COX-2) plays pivotal roles in many pathological processes including tumorigenesis and endometriosis, although the underlying mechanism remains obscure. Herein we report evidence to demonstrate that COX-2 is distinctly regulated by IL-1beta in normal and endometriotic stroma. Ectopic endometriotic stromal cell is at least 100 times more sensitive to IL-1beta treatment, compared with its eutopic counterpart. Induction of COX-2 expression in normal endometrial stroma by IL-1beta is primary due to enhancement of COX-2 mRNA stability. In contrast, IL-1beta not only increases COX-2 mRNA stability but also up-regulates COX-2 promoter activity in ectopic endometriotic stroma. Induction of COX-2 promoter activity by IL-1beta is mediated via MAPK-dependent phosphorylation of cAMP-responding element binding protein. Promoter activity and EMSAs demonstrate that a cAMP response element site located at -571/-564 of COX-2 promoter is critical for IL-1beta-induced COX-2 gene expression. Our results indicate that elevation of COX-2 expression in endometriotic tissues may result from increased sensitivity to proinflammatory cytokines such as IL-1beta, which is consistently present in the peritoneal fluid of endometriosis patients. Distinct regulation of COX-2 gene by IL-1beta may play a critical role in pathophysiological processes such as cancer formation and endometriosis. Published 11 January 2005 in J Clin Endocrinol Metab, 90(1): 286-95.
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