The induction and suppression of prostaglandin H2 synthase (cyclooxygenase) in human monocytes

We report here that the bacterial lipopolysaccharide endotoxin induces human blood monocytes in a time- and dose-dependent manner to release prodigious amounts of prostaglandins with thromboxane A2, the major metabolite formed. Cells responded to as little as 1 ng/ml lipopolysaccharide to release pr...

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Bibliographic Details
Published in:The Journal of biological chemistry 1990-10, Vol.265 (28), p.16737-16740
Main Authors: Fu, J Y, Masferrer, J L, Seibert, K, Raz, A, Needleman, P
Format: Article
Language:English
Subjects:
Analytical, structural and metabolic biochemistry
Arachidonate 5-Lipoxygenase - blood
Biological and medical sciences
Calcimycin - pharmacology
Cell Separation
Cells, Cultured
Dexamethasone - pharmacology
Enzyme Induction
Enzymes and enzyme inhibitors
Fundamental and applied biological sciences. Psychology
Humans
Kinetics
Lipopolysaccharides - pharmacology
Methionine - metabolism
Monocytes - cytology
Monocytes - drug effects
Monocytes - enzymology
Oxidoreductases
Phospholipases - blood
Prostaglandin-Endoperoxide Synthases - biosynthesis
Prostaglandin-Endoperoxide Synthases - blood
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Summary:We report here that the bacterial lipopolysaccharide endotoxin induces human blood monocytes in a time- and dose-dependent manner to release prodigious amounts of prostaglandins with thromboxane A2, the major metabolite formed. Cells responded to as little as 1 ng/ml lipopolysaccharide to release prostaglandin E2 and thromboxane A2 with maximal stimulation at 10 micrograms/ml. Lipopolysaccharide was found to induce increased activity of cyclooxygenase enzyme without affecting the activities of phospholipase and thromboxane synthase or the formation of 5-lipoxygenase products (e.g. leukotriene B4). The glucocorticoid dexamethasone completely blocked the lipopolysaccharide-induced prostanoid release by inhibiting the activity of monocyte cyclooxygenase. Dexamethasone did not affect phospholipase and thromboxane synthase activities or leukotriene formation. Immunoprecipitation of [35S]methionine-labeled cyclooxygenase confirmed that the effect of lipopolysaccharide and dexamethasone on the monocyte prostanoid production could be attributed to an increase or decrease, respectively, in cellular cyclooxygenase de novo synthesis.
ISSN:0021-9258
1083-351X
DOI:10.1016/S0021-9258(17)44821-6