Regulation of Cyclooxygenase-2 Expression by Phospholipase D in Human Amnion-Derived WISH Cells

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)-1␤ elicited dose-dependent synthesis of cyclooxygenase-2 (COX-2) mRNA, protein, and their products, PGE 2 . Moreover, the treatment of [ 3 H]myristate-labeled cells in the presence of 1-butanol caused the dose-dependent formation of [ 3 H]phosphatidylbutanol (PBt), a product specific to PLD activity. Pretreating the cells with 1-butanol and Ro 31-8220 inhibited the IL-1␤-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-1␤. Moreover, IL-1␤ stimulation of the cells caused the phosphorylation of p38 and extracellular signalregulated kinase (ERK), and IL-1␤-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-1␤-induced p38 phosphorylation but not ERK phosphorylation. The results of this study indicate that in human amnion cells, IL-1␤ might activate PLD through an upstream protein kinase C to elicit p38 and finally induce COX-2 expression.

Prostacyclin production in rat aortic smooth muscle cells: role of protein kinase C, phospholipase D and cyclooxygenase-2 expression

“…These observations suggest that AngII-induced COX-2 expression and subsequent increase in PGI 2 production is to a great extent mediated by PA resulting from PLD activation. In agreement with our results, PLD was reported to be involved in the regulation of COX-2 expression in amnion-derived WISH cells stimulated by interleukin-1h [13] and phorbol ester [12].…”

“…Two studies provide evidence that PGI 2 synthesis is limited by the expression levels of COX-2, and that there is a link between PLD and interleukin-1h-and PMA-stimulated PGI 2 production in amnionic WISH cells [12,13], but there is no information concerning this link in VSMC. In this study, we investigated the possible role of PKC and PLD activation in AngIIand PMA-induced COX-2 expression and PGI 2 secretion in VSMC.…”

The Mitogen-Activated Protein Kinase Dependent Expression of Prostaglandin H Synthase-2 and Interleukin-8 Messenger Ribonucleic Acid by Myometrial Cells: The Differential Effect of Stretch and Interleukin-1β

“…Its production is increased in myometrium, cervix, decidua, and fetal membranes with labor (4, 10), and its levels are increased in amniotic fluid in the presence of chorioamnionitis and with the duration of labor (11,12). It acts synergistically with IL-8 to increase prostaglandin production and uterine contractions in the rabbit (7), and in vitro in human myometrial cells, it increases prostaglandin H synthase 2 (PGHS-2) expression via p38 MAPK activation and increased nuclear factor B (NFB) DNA binding in myometrium and amnion (13)(14)(15). IL-1␤ also increases IL-8 expression in fetal membranes and lower segment fibroblasts (8) and reduces prostaglandin dehydrogenase activity in the intact fetal membrane disc model (16).…”

Phosphatidic acid induces the differentiation of human acute promyelocytic leukemic cells into dendritic cell‐like

“…1C). Exogenous PA (100-500 mM) has been shown to have various biological functions [MurakamiMurofushi et al, 2002;Park et al, 2002;Sakai et al, 2002]. PA alone did not affect the viability of the cells nor did it induce apoptosis of NB4, as measured on Day 3 (data not shown).…”