Induction of both cytosolic phospholipase A 2 and prostaglandin H synthase-2 by interleukin-1 β in WISH cells is inhibited by dexamethasone

Abstract

In previous studies we have shown that IL-1β induced both PGE 2 release and total cellular cPLA 2 activity and cPLA 2 protein synthesis in human amnion-derived WISH cells. In this study, the effect of IL-1β on cPLA 2 and PGHS-2 mRNA expression was investigated. Using RT-PCR, we found that IL-1β (0.1 ng/ml) coordinately induced both cPLA 2 and PGHS-2 mRNA expression within 2 hours. The synthetic glucocorticoid dexamethasone (10 −10−10 −6M) inhibited IL-1β-induced cPLA 2 and PGHS-2 mRNA expression activity and protein synthesis and PGE 2 release in a concentration dependent manner. In the absence of IL-1β, dexamethasone alone (10 −6M) inhibited basal CPLA 2 activity, mRNA expression and protein synthesis. In addition, cycloheximide (5 μg/ml) apparently superinduced, but actinomycin D (2 μg/ml) inhibited IL-1β-induced cPLA 2 and PGHS-2 mRNA expression suggesting that both are immediate early genes and a transcriptional mechanism is involved in the induction of both cPLA 2 and PGHS-2 mRNA by IL-1β.