Regulation of cyclooxygenase and thromboxane synthase in human monocytes.
Stimulation of human monocytes by lipopolysaccharide or phorbol ester resulted in an increase in thromboxane-B2 and prostaglandin-E2 production, whereas interleukin 1, tumour necrosis factor alpha and leukotriene C4 exerted no effects. Inhibitors of protein kinase C suppressed these increases. The activity of cyclooxygenase was induced 3.2-fold by an 8-h stimulation, whereas thromboxane-synthase and prostaglandin-E-isomerase activities remained unchanged. A glucocorticoid, dexamethasone, blocked both basal and induced prostanoid release, as well as cyclooxygenase activity. By immunoprecipitation, we were able to demonstrate an enhanced de novo synthesis of cyclooxygenase protein induced by lipopolysaccharide and phorbol ester. Dexamethasone suppressed cyclooxygenase synthesis, whereas thromboxane synthase was induced. For cyclooxygenase, we calculated a half-life of 3.2 h in human monocytes, and for thromboxane synthase, a half-life of 28 h. These results suggest that the regulation of differential prostanoid production mainly occurs by up and down regulation of cyclooxygenase.
Nüsing
R
R
Faculty of Biology, University of Konstanz, Federal Republic of Germany.
Ullrich
V
V
D002478:Cells, Cultured; D003609:Dactinomycin / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology; D007700:Kinetics; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000201:enzymology*; D008070:Lipopolysaccharides; D011451:Prostaglandin-Endoperoxide Synthases / Q000097:blood*; D011453:Prostaglandins / Q000096:biosynthesis / Q000097:blood; D013189:SRS-A / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013930:Thromboxane-A Synthase / Q000097:blood*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D007375:Interleukin-1; D008070:Lipopolysaccharides; D011453:Prostaglandins; D013189:SRS-A; D014409:Tumor Necrosis Factor-alpha; D003609:Dactinomycin; D003907:Dexamethasone; D011451:Prostaglandin-Endoperoxide Synthases; D013930:Thromboxane-A Synthase; D013755:Tetradecanoylphorbol Acetate