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

Objective: To 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 methods: Human amnion fibroblasts were prepared from fetal amnion collected at term and were treated with dexamethasone with or without interleukin-1β for 24h. 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. Results: Both 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. Conclusion: The 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. [Copyright &y& Elsevier]