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https://hdl.handle.net/2440/11554
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Type: | Journal article |
Title: | Expression and activity of prostoglandin endoperoxide synthase-2 in inflammatory human neutrophils |
Author: | Pouliot, M. Gilbert, C. Borgeat, P. Poubelle, P. Bourgoin, S. McColl, S. Naccache, P. |
Citation: | The FASEB Journal, 1998; 12(12):1109-1123 |
Publisher: | FEDERATION AMER SOC EXP BIOL |
Issue Date: | 1998 |
ISSN: | 0892-6638 1530-6860 |
Abstract: | Proinflammatory 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. |
Keywords: | Neutrophils Humans Escherichia coli Tetradecanoylphorbol Acetate Isoenzymes Lipopolysaccharides Zymosan N-Formylmethionine Leucyl-Phenylalanine Tumor Necrosis Factor-alpha Granulocyte-Macrophage Colony-Stimulating Factor Membrane Proteins Antibodies Epitopes Blotting, Western Signal Transduction Phagocytosis Transcription, Genetic Gene Expression Regulation, Enzymologic Amino Acid Sequence Molecular Sequence Data Prostaglandin-Endoperoxide Synthases Cyclooxygenase 2 In Vitro Techniques |
DOI: | 10.1096/fasebj.12.12.1109 |
Published version: | http://www.fasebj.org/content/12/12/1109.abstract |
Appears in Collections: | Aurora harvest 2 Microbiology and Immunology publications |
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