1,25-dihydroxyvitamin D3 induces NAD(+)-dependent 15-hydroxyprostaglandin dehydrogenase in human neonatal monocytes.
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.
Pichaud
F
F
U. 349 and U. 348 INSERM, Hôpital Lariboisière, centre Viggo Petersen, Paris, France.
Roux
S
S
Frendo
J L
JL
Delage-Mourroux
R
R
Maclouf
J
J
de Vernejoul
M C
MC
Moukhtar
M S
MS
Jullienne
A
A
D000328:Adult; D002117:Calcitriol / Q000494:pharmacology*; D003470:Culture Media; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000032:analysis; D004789:Enzyme Activation; D004790:Enzyme Induction; D005312:Fetal Blood / Q000737:chemistry / Q000201:enzymology*; D006801:Humans; D006911:Hydroxyprostaglandin Dehydrogenases / Q000096:biosynthesis* / Q000235:genetics / Q000302:isolation & purification; D007527:Isoenzymes / Q000235:genetics; D008565:Membrane Proteins; D009000:Monocytes / Q000737:chemistry / Q000201:enzymology*; D009243:NAD / Q000502:physiology; D016133:Polymerase Chain Reaction; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis
D003470:Culture Media; D007527:Isoenzymes; D008565:Membrane Proteins; D012333:RNA, Messenger; D009243:NAD; D006911:Hydroxyprostaglandin Dehydrogenases; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D002117:Calcitriol; D015232:Dinoprostone