Induction of both cytosolic phospholipase A2 and prostaglandin H synthase-2 by interleukin-1 beta in WISH cells in inhibited by dexamethasone.
In previous studies we have shown that IL-1 beta induced both PGE2 release and total cellular cPLA2 activity and cPLA2 protein synthesis in human amnion-derived WISH cells. In this study, the effect of IL-1 beta on cPLA2 and PGHS-2 mRNA expression was investigated. Using RT-PCR, we found that IL-1 beta (0.1 ng/ml) coordinately induced both cPLA2 and PGHS-2 mRNA expression within 2 hours. The synthetic glucocorticoid dexamethasone (10(-10)-10(-6)M) inhibited IL-1 beta-induced cPLA2 and PGHS-2 mRNA expression activity and protein synthesis and PGE2 release in a concentration dependent manner. In the absence of IL-1 beta, dexamethasone alone (10(-6)M) inhibited basal cPLA2 activity, mRNA expression and protein synthesis. In addition, cycloheximide (5 micrograms/ml) apparently superinduced, but actinomycin D (2 micrograms/ml) inhibited IL-1 beta-induced cPLA2 and PGHS-2 mRNA expression suggesting that both are immediate early genes and a transcriptional mechanism is involved in the induction of both cPLA2 and PGHS-2 mRNA by IL-1 beta.
Xue
S
S
Department of Obstetrics and Gynecology, University of Cincinnati College of Medicine, OH 45267-0526, USA.
Slater
D M
DM
Bennett
P R
PR
Myatt
L
L
D000650:Amnion / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D001483:Base Sequence; D002460:Cell Line; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D003600:Cytosol / Q000187:drug effects / Q000201:enzymology; D003907:Dexamethasone / Q000494:pharmacology*; D015232:Dinoprostone / Q000096:biosynthesis; D004790:Enzyme Induction; D005938:Glucocorticoids / Q000494:pharmacology*; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000037:antagonists & inhibitors*; D008969:Molecular Sequence Data; D010741:Phospholipases A / Q000096:biosynthesis* / Q000235:genetics; D054467:Phospholipases A2; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis
D016861:Cyclooxygenase Inhibitors; D005938:Glucocorticoids; D007375:Interleukin-1; D012333:RNA, Messenger; D003907:Dexamethasone; D011451:Prostaglandin-Endoperoxide Synthases; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D010741:Phospholipases A; D054467:Phospholipases A2; D015232:Dinoprostone