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1,25-dihydroxyvitamin D3 induces NAD(+)-dependent 15- hydroxyprostaglandin dehydrogenase in human neonatal monocytes

F Pichaud, S Roux, JL Frendo, R Delage-Mourroux, J Maclouf, MC de Vernejoul, MS Moukhtar and A Jullienne

U. 349 and U. 348 INSERM, Hopital Lariboisiere, centre Viggo Petersen, Paris, France.

1,25-Dihydroxyvitamin D3 [1,25-(OH)2D3] 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)2D3. Treated CBMs expressed type-I 15- hydroxyprostaglandin dehydrogenase (type-I 15-PGDH), the key enzyme of prostaglandin E2 (PGE2) 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 PGE2 levels in the culture mediums were lowered (50%). Our results stress that 1,25-(OH)2D3, at least in neonatal monocytes, can exert, directly or indirectly, a dual control on key enzymes of PGE2 metabolism. In conclusion, we suggest that modifications in prostaglandin metabolism, induced by the expression of type-I 15-PGDH and the downregulation of cyclooxygenase 2, could be involved in monocytic differentiation.

Volume 89, Issue 6, pp. 2105-2112, 03/15/1997
Copyright © 1997 by The American Society of Hematology


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