PT  - JOURNAL ARTICLE
AU  - Park, Dae-Won
AU  - Bae, Yoe-Sik
AU  - Nam, Ju-Ock
AU  - Kim, Jong-Ho
AU  - Lee, Young-Gi
AU  - Park, Yoon-Ki
AU  - Ryu, Sung Ho
AU  - Baek, Suk-Hwan
TI  - Regulation of Cyclooxygenase-2 Expression by Phospholipase D in Human Amnion-Derived WISH Cells
AID  - 10.1124/mol.61.3.614
DP  - 2002 Mar 01
TA  - Molecular Pharmacology
PG  - 614--619
VI  - 61
IP  - 3
4099  - http://molpharm.aspetjournals.org/content/61/3/614.short
4100  - http://molpharm.aspetjournals.org/content/61/3/614.full
SO  - Mol Pharmacol2002 Mar 01; 61
AB  - 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–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–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–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.