Dexamethasone induces lipocalin-type prostaglandin D synthase gene expression in mouse neuronal cells.
Lipocalin-type prostaglandin (PG) D synthase (L-PGDS) is responsible for the production of PGD(2), the main PG in the CNS. PGD(2) is an endogenous sleep inducer, and it is involved in the control of odor and pain responses and body temperature. In addition, PGD synthase transports lipophilic molecules in the subarachnoid space and CSF. By northern and western assays we show that the synthetic glucocorticoid dexamethasone, an inhibitor of PG production in most tissues, induces L-PGDS mRNA and protein in a dose- and time-dependent fashion in mouse neuronal GT1-7 cells. Accordingly, dexamethasone increases cellular L-PGDS enzymatic activity. Dexamethasone induced L-PGDS gene transcription in run-on assays and activated the mouse L-PGDS gene promoter in transiently transfected cells. It is interesting that the tumor promoter 12-O-tetradecanoyl-phorbol 13-acetate (TPA), which induces the synthesis of PGs in many tissues, inhibited the increase in L-PGDS expression induced by dexamethasone. In contrast, neither dexamethasone nor TPA affected the expression of cyclooxygenases-1 and -2. Our data demonstrate that dexamethasone induces L-PGDS gene transcription in neuronal cells.
García-Fernández
L F
LF
Instituto de Investigaciones Biomédicas "Alberto Sols" Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid, Madrid, Spain.
Iñiguez
M A
MA
Eguchi
N
N
Fresno
M
M
Urade
Y
Y
Muñoz
A
A
D000818:Animals; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D003907:Dexamethasone / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D017930:Genes, Reporter; D019746:Intramolecular Oxidoreductases / Q000235:genetics*; D007700:Kinetics; D054834:Lipocalins; D051379:Mice; D009474:Neurons / Q000201:enzymology*; D014176:Protein Biosynthesis / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection
D054834:Lipocalins; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D003907:Dexamethasone; D015500:Chloramphenicol O-Acetyltransferase; D019746:Intramolecular Oxidoreductases; C022466:prostaglandin R2 D-isomerase; D013755:Tetradecanoylphorbol Acetate