Regulation of cyclooxygenase-2 expression by phospholipase D in human amnion-derived WISH cells
SCIE
SCOPUS
- Title
- Regulation of cyclooxygenase-2 expression by phospholipase D in human amnion-derived WISH cells
- Authors
- Park, DW; Bae, YS; Nam, JO; Kim, JH; Lee, YG; Park, YK; Ryu, SH; Baek, SH
- Date Issued
- 2002-03
- Publisher
- AMER SOC PHARMACOLOGY EXPERIMENTAL TH
- Abstract
- Prostaglandins (PGs) are known to play a key role in the initiation of labor, but the mechanisms regulating their synthesis in amnion are largely unknown. In this study, the regulatory mechanisms for PGE(2) production during phospholipase D (PLD) and p38-dependent activation of WISH cells were investigated. We found that the stimulation of WISH cells with interleukin (IL)-1beta elicited dose-dependent synthesis of cyclooxygenase-2 (COX-2) mRNA, protein, and their products, PGE(2). Moreover, the treatment of [H-3]myristate-labeled cells in the presence of 1-butanol caused the dose-dependent formation of [H-3]phosphatidylbutanol (PBt), a product specific to PLD activity. Pre-treating the cells with 1-butanol and Ro 31-8220 inhibited the IL-1beta-induced COX-2 expression, but 3-butanol did not affect this response. In addition, evidence that PLD was involved in the stimulation of COX-2 expression was provided by the observations that COX-2 expression was stimulated by the dioctanoyl phosphatidic acid (PA) and that the prevention of PA dephosphorylation by 1-propranolol potentiated COX-2 expression by IL-1beta. Moreover, IL-1beta stimulation of the cells caused the phosphorylation of p38 and extracellular signal-regulated kinase (ERK), and IL-1beta-induced COX-2 expression was inhibited by the pretreatment of WISH cells with a p38 inhibitor, in contrast ERK upstream inhibitor had no effect. Furthermore, Ro 31-8220 inhibited IL-1beta-induced p38 phosphorylation but not ERK phosphorylation. The results of this study indicate that in human amnion cells, IL-1beta might activate PLD through an upstream protein kinase C to elicit p38 and finally induce COX-2 expression.
- Keywords
- PROTEIN-KINASE-C; EPIDERMAL GROWTH-FACTOR; PROSTAGLANDIN E-2; SPONTANEOUS LABOR; PLASMA-MEMBRANE; PHORBOL ESTER; INTERLEUKIN-1-BETA; INVOLVEMENT; ACTIVATION; TERM
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/19189
- DOI
- 10.1124/mol.61.3.614
- ISSN
- 0026-895X
- Article Type
- Article
- Citation
- MOLECULAR PHARMACOLOGY, vol. 61, no. 3, page. 614 - 619, 2002-03
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