Results
| PMID | 15483103 |
| Gene Name | IL1B |
| Condition | Endometriosis |
| Association |
Associated |
| Sex | Female |
| Associated genes | IL-1beta, COX-2 |
| Other associated phenotypes |
Endometriosis |
|
J Clin Endocrinol Metab. 2005 Jan;90(1):286-95. Epub 2004 Oct 13. Wu, Meng-Hsing| Wang, Chu-An| Lin, Chen-Chung| Chen, Lei-Chin| Chang, Wen-Chang| Tsai, Shaw-Jenq 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. Mesh Terms: Cells, Cultured| Cyclic AMP Response Element-Binding Protein/metabolism| Cyclooxygenase 2| Endometriosis/*enzymology| Female| Gene Expression Regulation, Enzymologic/*drug effects| Humans| Interleukin-1/*pharmacology| Isoenzymes/*genetics| Membra |
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