Proinflammatory cytokines regulate cyclooxygenase-2 mRNA expression in human macrophages.
Prostaglandins play a major role in the inflammatory and immune response. Macrophages constitutively produce prostaglandins by the enzyme cyclooxygenase-1 (cox) whereas inflammatory mediators and cytokines stimulate the inducible enzyme cox-2 for high output prostaglandin production. In this study, we investigated the effect of LPS, IFN-gamma and TNF-alpha in the regulation of cox-1 and cox-2 mRNA expression in PMA-differentiated U937 human macrophages. LPS, but not IFN-gamma or TNF-alpha, caused the induction of cox-2 mRNA in a dose- and time-dependent fashion. In IFN-gamma-primed macrophages, LPS stimulated a marked increase in the accumulation of cox-2 mRNA, whereas TNF-alpha and IFN-gamma induced a moderate level. However, IFN-gamma in combination with either LPS or TNF-alpha induced a synergistic increase in the accumulation of cox-2 mRNA after 24 hours. Regardless of the conditions, cox-1 mRNA remained unchanged. These results indicate that IFN-gamma priming is required for full expression of cox-2 mRNA in response to LPS or TNF-alpha stimulation and suggest that cox-2 mRNA is highly regulated by cytokines during macrophage activation.
Arias-Negrete
S
S
Institute of Parasitology, McGill University, Ste-Anne de Bellevue, Québec, Canada.
Keller
K
K
Chadee
K
K
D002478:Cells, Cultured; D004790:Enzyme Induction; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000494:pharmacology*; D007527:Isoenzymes / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000201:enzymology*; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D007527:Isoenzymes; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D011451:Prostaglandin-Endoperoxide Synthases