@article {Park614, author = {Dae-Won Park and Yoe-Sik Bae and Ju-Ock Nam and Jong-Ho Kim and Young-Gi Lee and Yoon-Ki Park and Sung Ho Ryu and Suk-Hwan Baek}, title = {Regulation of Cyclooxygenase-2 Expression by Phospholipase D in Human Amnion-Derived WISH Cells}, volume = {61}, number = {3}, pages = {614--619}, year = {2002}, doi = {10.1124/mol.61.3.614}, publisher = {American Society for Pharmacology and Experimental Therapeutics}, 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 PGE2 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)-1β elicited dose-dependent synthesis of cyclooxygenase-2 (COX-2) mRNA, protein, and their products, PGE2. Moreover, the treatment of [3H]myristate-labeled cells in the presence of 1-butanol caused the dose-dependent formation of [3H]phosphatidylbutanol (PBt), a product specific to PLD activity. Pretreating the cells with 1-butanol and Ro 31-8220 inhibited the IL-1β{\textendash}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-1β. Moreover, IL-1β stimulation of the cells caused the phosphorylation of p38 and extracellular signal-regulated kinase (ERK), and IL-1β{\textendash}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-1β{\textendash}induced p38 phosphorylation but not ERK phosphorylation. The results of this study indicate that in human amnion cells, IL-1β might activate PLD through an upstream protein kinase C to elicit p38 and finally induce COX-2 expression.}, issn = {0026-895X}, URL = {https://molpharm.aspetjournals.org/content/61/3/614}, eprint = {https://molpharm.aspetjournals.org/content/61/3/614.full.pdf}, journal = {Molecular Pharmacology} }