Dexamethasone fails to inhibit the induction of cytosolic phospholipase A(2) expression by interleukin-1beta in cultured primary human amnion fibroblasts.
OBJECTIVE
To investigate the interaction of dexamethasone and interleukin-1beta (IL-1beta) on the expression of cytosolic phospholipase A(2) (cPLA(2)), the enzyme catalyzing the first reaction in the formation of prostaglandins, in cultured primary human amnion fibroblasts.


METHODS
Human amnion fibroblasts were prepared from fetal amnion collected at term and were treated with dexamethasone with or without interleukin-1beta for 24h. Prostaglandin E(2) (PGE(2)) output and cPLA(2) expression in cultured amnion fibroblasts were measured with radioimmunoassay, quantitative real-time polymerase chain reaction, Western blotting and cPLA(2) promoter-driven luciferase reporter gene activity.


RESULTS
Both dexamethasone and IL-1beta caused a significant increase in prostaglandin E(2) output, cPLA(2) mRNA and protein expression in cultured human amnion fibroblasts. Both dexamethasone and IL-1beta stimulated cPLA(2) promoter-driven luciferase reporter gene activity. There was no obvious antagonistic or synergistic effect of combined treatment of dexamethasone and IL-1beta on PGE(2) output, cPLA(2) expression or cPLA(2) promoter-driven luciferase reporter gene activity in cultured human amnion fibroblasts.


CONCLUSIONS
The above findings suggest that paradoxically dexamethasone is a stimulator for both prostaglandin synthesis and cPLA(2) expression in human amnion fibroblasts. The interaction between dexamethasone and IL-1beta on prostaglandin synthesis and cPLA(2) expression is neither synergistic nor conventionally antagonistic.
Sun
K
K
Department of Physiology and Biophysics, School of Life Sciences, Fudan University, Second Military Medical University, 220 Handan Road, Shanghai 200433, P.R. China. sunnygangsun@yahoo.com.cn
Qu
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X
Gao
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Myatt
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D000650:Amnion / Q000166:cytology* / Q000187:drug effects* / Q000201:enzymology; D002478:Cells, Cultured; D003600:Cytosol / Q000201:enzymology; D003907:Dexamethasone / Q000494:pharmacology*; D015232:Dinoprostone / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000201:enzymology; D017930:Genes, Reporter; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D008156:Luciferases / Q000032:analysis / Q000235:genetics; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic
D007375:Interleukin-1; D003907:Dexamethasone; D008156:Luciferases; D010741:Phospholipases A; D015232:Dinoprostone