Cyclooxygenase is an immediate-early gene induced by interleukin-1 in human endothelial cells.
The monokine interleukin-1 (IL-1) inhibits endothelial cell growth and induces prostacyclin production in human endothelial cells. Since cyclooxygenase (Cox) is the rate-limiting enzyme in the synthesis of prostanoids, we evaluated the ability of IL-1 to stimulate Cox expression by human umbilical vein endothelial cells (HUVEC) in vitro. Our data demonstrate that 1) the Cox mRNA is expressed at low levels in untreated cells; 2) IL-1 alpha induces the Cox mRNA within 2 h, and this induction is sustained for more than 24 h; 3) IL-1 alpha induction is dose-dependent; 4) cycloheximide potentiates the induction of the Cox mRNA by IL-1 alpha while actinomycin D prevents the induction, and 5) IL-1 alpha also stimulates Cox production in a time-dependent fashion which correlates with the increase in prostacyclin synthesis. These data suggest that Cox is an immediate-early gene induced by IL-1 in HUVEC and may contribute to the regulation of the endothelial cell differentiation pathway in vitro.
Maier
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Jerome H. Holland Laboratory for the Biomedical Sciences, American Red Cross, Rockville, Maryland 20855.
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D015153:Blotting, Western; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004357:Drug Synergism; D004730:Endothelium, Vascular / Q000201:enzymology*; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D007700:Kinetics; D009693:Nucleic Acid Hybridization; D016133:Polymerase Chain Reaction; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics*; D011453:Prostaglandins / Q000096:biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D012194:RNA-Directed DNA Polymerase; D014158:Transcription, Genetic; D014471:Umbilical Veins
D007375:Interleukin-1; D011453:Prostaglandins; D012333:RNA, Messenger; D003609:Dactinomycin; D003513:Cycloheximide; D011451:Prostaglandin-Endoperoxide Synthases; D012194:RNA-Directed DNA Polymerase