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|Title:||Expression and activity of prostoglandin endoperoxide synthase-2 in inflammatory human neutrophils|
|Citation:||FASEB Journal, 1998; 12(12):1109-1123|
|Publisher:||FEDERATION AMER SOC EXP BIOL|
|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|
|Appears in Collections:||Microbiology and Immunology publications|
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