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

Ji Yi Fu*, Jaime L. Masferrer, Karen Seibert, Amiram Raz, Philip Needleman

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

937 Scopus citations

Abstract

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 μg/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.

Original languageEnglish
Pages (from-to)16737-16740
Number of pages4
JournalJournal of Biological Chemistry
Volume265
Issue number28
StatePublished - 5 Oct 1990
Externally publishedYes

Funding

FundersFunder number
National Heart, Lung, and Blood InstituteR01HL020787
National Institute of Diabetes and Digestive and Kidney DiseasesP01DK038111

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