1,25-dihydroxyvitamin D-3 induces NAD((+))-dependent 15-hydroxyprostaglandin dehydrogenase in human neonatal monocytes

1,25-Dihydroxyvitamin D-3 [1,25-(OH)(2)D-3] induces the differentiation of monocytes into macrophage-like cells in vitro. To identify the genes expressed during this process, we performed differential display polymerase chain reaction on RNA extracted from cord blood monocytes (CBMs) treated with 1,25-(OH)(2)D-3. Treated CBMs expressed type-1 15-hydroxyprostaglandin dehydrogenase (type-1 15-PGDH), the key enzyme of prostaglandin E(2) (PGE(2)) catabolism and a 15-PGDH-related mRNA (15-PGDHr). This newly described 15-PGDH-related mRNA was constitutively expressed in adult monocytes. 15-PGDH gene(s) transcription was accompanied by the appearance of the 15-PGDH activity in treated CBMs. In addition, the cyclooxygenase 2 mRNA level was decreased and PGE(2) levels in the culture mediums were lowered (50%). Our results stress that 1,25-(OH)(2)D-3, at least in neonatal monocytes, can exert, directly or indirectly, a dual control on key enzymes of PGE(2) metabolism. In conclusion, we suggest that modifications in prostaglandin metabolism, induced by the expression of type-1 15-PGDH and the downregulation of cyclooxygenase 2, could be involved in monocytic differentiation. (C) 1997 by The American Society of Hematology.