Nonsteroidal antiinflammatory drugs inhibit cyclooxygenase-2 enzyme activity but not mRNA expression in human macrophages.
At present it is unclear whether nonsteroidal antiinflammatory drugs (NSAIDs) can inhibit cyclooxygenase (COX) gene expression. In some cells that express COX-2, NSAIDs can inhibit enzymatic activity and gene expression. In this study we evaluated the effect of several NSAIDs on COX-1 and COX-2 mRNA, protein expression and PGE2 production in PMA-differentiated THP-1 and U937 human macrophages stimulated with LPS. Macrophages pre-treated with acetylsalicylic acid, indomethacin, naproxen or NS-398 and stimulated with LPS showed a marked inhibition on PGE2 production but not on COX-1 or COX-2 mRNA and protein expression. Furthermore, COX-2 mRNA levels induced by LPS were transient (peak 3-4 h), suggesting that PGE2 was unable to regulate COX-2 expression in an autocrine manner. These results demonstrate that NSAID's action in human macrophages is not directed towards the transcription or translation of the COX genes but only to the enzymatic activity of the proteins.
Barrios-Rodiles
M
M
Institute of Parasitology of McGill University, Quebec, Canada.
Keller
K
K
Belley
A
A
Chadee
K
K
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology; D002460:Cell Line; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007527:Isoenzymes / Q000235:genetics* / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology*; D008565:Membrane Proteins; D009288:Naproxen / Q000494:pharmacology; D009578:Nitrobenzenes / Q000494:pharmacology; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics* / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism*; D013449:Sulfonamides / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D007527:Isoenzymes; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D009578:Nitrobenzenes; D012333:RNA, Messenger; D013449:Sulfonamides; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D009288:Naproxen; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D001241:Aspirin; D007213:Indomethacin