NONSTEROIDAL ANTIINFLAMMATORY DRUGS INHIBIT CYCLOOXYGENASE-2 ENZYME-ACTIVITY BUT NOT MESSENGER-RNA EXPRESSION IN HUMAN MACROPHAGES

At present it is unclear whether nonsteroidal antiinflammatory drugs ( NSAIDs) can inhibit cyclooxygenase (COX) gene expression. In some cell s that express COX-2, NSAIDs can inhibit enzymatic activity and gene e xpression. In this study we evaluated the effect of several NSAIDs on COX-1 and COX-2 mRNA, protein expression and PGE(2) production in PMA- differentiated THP-1 and U937 human macrophages stimulated with LPS. M acrophages pre-treated with acetylsalicylic acid, indomethacin, naprox en or NS-398 and stimulated with LPS showed a marked inhibition on PGE (2) 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 PGE(2) 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 transl ation of the COX genes but only to the enzymatic activity of the prote ins. (C) 1996 Academic Press, Inc.