Dexamethasone Fails to Inhibit the Induction of Cytosolic Phospholipase A2 Expression by Interleukin-1β in Cultured Primary Human Amnion Fibroblasts

ObjectiveTo investigate the interaction of dexamethasone and interleukin-1β (IL-1β) on the expression of cytosolic phospholipase A2 (cPLA2), the enzyme catalyzing the first reaction in the formation of prostaglandins, in cultured primary human amnion fibroblasts.Design and methodsHuman amnion fibroblasts were prepared from fetal amnion collected at term and were treated with dexamethasone with or without interleukin-1β for 24 h. Prostaglandin E2 (PGE2) output and cPLA2 expression in cultured amnion fibroblasts were measured with radioimmunoassay, quantitative real-time polymerase chain reaction, Western blotting and cPLA2 promoter-driven luciferase reporter gene activity.ResultsBoth dexamethasone and IL-1β caused a significant increase in prostaglandin E2 output, cPLA2 mRNA and protein expression in cultured human amnion fibroblasts. Both dexamethasone and IL-1β stimulated cPLA2 promoter-driven luciferase reporter gene activity. There was no obvious antagonistic or synergistic effect of combined treatment of dexamethasone and IL-1β on PGE2 output, cPLA2 expression or cPLA2 promoter-driven luciferase reporter gene activity in cultured human amnion fibroblasts.ConclusionThe above findings suggest that paradoxically dexamethasone is a stimulator for both prostaglandin synthesis and cPLA2 expression in human amnion fibroblasts. The interaction between dexamethasone and IL-1β on prostaglandin synthesis and cPLA2 expression is neither synergistic nor conventionally antagonistic.