Indomethacin increases 15-PGDH mRNA expression in HL60 cells differentiated by PMA

We previously reported an induction of 15-hydroxyprostaglandin dehydrogenas e type I mRNA (15-PGDH) expression accompanied by a decrease in prostagland in E-2 (PGE(2)) levels during cord blood monocytes differentiation into pre osteoclastic cells by 1,25 dihydroxyvitamin D3 (1,25 (OH)(2)D-3). These res ults suggested a role of prostaglandin (PG) enzymes in adhesion and/or diff erentiation of monocytes. In the present work, we studied modulation of gene expression of PG metabol ism enzymes mRNAs in HL60 cells differentiated by phorbol myristate acetate (PMA) into the monocyte/macrophage lineage. We showed that adhesion of HL6 0 induced by PMA causes an increase of cyclooxygenase 2 (COX 2) and 15-PGDH mRNAs. When adding indomethacin, a non steroidal antiinflammatory drug kno wn to inhibit COX activity, the cells remained attached and expressed large amounts of 15-PGDH mRNA while COX 2 mRNA expression remained unchanged. In domethacin, in association with PMA can consequently exert a dual control o n key enzymes of PGE(2) metabolism without modifying adhesion of the cells. (C) 2001 Harcourt Publishers Ltd.