Expression and activity of prostoglandin endoperoxide synthase-2 in inflammatory human neutrophils

Simple item page
dc.contributor.authorPouliot, M.
dc.contributor.authorGilbert, C.
dc.contributor.authorBorgeat, P.
dc.contributor.authorPoubelle, P.
dc.contributor.authorBourgoin, S.
dc.contributor.authorMcColl, S.
dc.contributor.authorNaccache, P.
dc.date.issued1998
dc.description.abstractProinflammatory agents were assessed for their capacity to stimulate the expression of the inducible cyclooxygenase isoform (COX-2) in human neutrophils. A number of agents, including PMA, opsonized bacteria and zymosan, LPS, GM-CSF, TNF-alpha, and fMLP, induced COX-2 protein expression through signaling pathways involving transcription and protein synthesis events. Northern blots showed that freshly isolated neutrophils expressed low levels of COX-2 mRNA, which rapidly increased after incubation with inflammatory agents. A characterization of the signal transduction pathways leading to COX-2 protein expression was initiated. In LPS-treated neutrophils, efficient induction of COX-2 required the presence of serum and involved ligand binding to the CD14 surface antigen. The specific inhibitor of p38 mitogen-activated protein kinase (p38 MAPK), SB 203580, had little effect on the induction of COX-2 expression in neutrophils, in contrast to what had been previously observed with other inflammatory cell types. Depending on the agonist present, ethanol differentially blocked the stimulated expression of COX-2, raising the possibility that phospholipase D activation might take part in the process of COX-2 induction. Major COX-2-derived prostanoids synthesized by inflammatory neutrophils were identified by liquid-chromatography and tandem mass-spectrometry as TXA2 and PGE2. The agonist-induced synthesis of TXA2 and PGE2 was effectively blocked by cycloheximide and by the specific COX-2 inhibitor NS-398. These results show that COX-2 can be induced in an active state by different classes of inflammatory mediators in the neutrophil. They support the concept that, in these cells, the COX-2 isoform is preeminent over COX-1 for the stimulated-production of prostanoids, and also suggest that neutrophil COX-2 displays a distinct profile of expression among circulatory cells.
dc.identifier.citationThe FASEB Journal, 1998; 12(12):1109-1123
dc.identifier.doi10.1096/fasebj.12.12.1109
dc.identifier.issn0892-6638
dc.identifier.issn1530-6860
dc.identifier.orcidMcColl, S. [0000-0003-0949-4660]
dc.identifier.urihttp://hdl.handle.net/2440/11554
dc.language.isoen
dc.publisherWILEY
dc.source.urihttp://www.fasebj.org/content/12/12/1109.abstract
dc.subjectNeutrophils
dc.subjectHumans
dc.subjectEscherichia coli
dc.subjectTetradecanoylphorbol Acetate
dc.subjectIsoenzymes
dc.subjectLipopolysaccharides
dc.subjectZymosan
dc.subjectN-Formylmethionine Leucyl-Phenylalanine
dc.subjectTumor Necrosis Factor-alpha
dc.subjectGranulocyte-Macrophage Colony-Stimulating Factor
dc.subjectMembrane Proteins
dc.subjectAntibodies
dc.subjectEpitopes
dc.subjectBlotting, Western
dc.subjectSignal Transduction
dc.subjectPhagocytosis
dc.subjectTranscription, Genetic
dc.subjectGene Expression Regulation, Enzymologic
dc.subjectAmino Acid Sequence
dc.subjectMolecular Sequence Data
dc.subjectProstaglandin-Endoperoxide Synthases
dc.subjectCyclooxygenase 2
dc.subjectIn Vitro Techniques
dc.titleExpression and activity of prostoglandin endoperoxide synthase-2 in inflammatory human neutrophils
dc.typeJournal article
pubs.publication-statusPublished

Files

Collections

Microbiology and Immunology publications