FK506 (tacrolimus) increases rat alpha1-acid glycoprotein expression in liver and primary cultured hepatocytes.
FK506 (tacrolimus) (10 mg/kg, s.c., 5 days) increased rat alpha1-acid glycoprotein (AGP) in serum and AGP mRNA in liver. FK506 potentiated the dexamethasone-increased AGP expression in primary cultured hepatocytes. In the luciferase promoter assay, FK506 potentiated the dexamethasone-increased promoter activity of the AGP gene in cultured rat hepatocytes, although FK506 alone had no effect on its activity. The combined effect of FK506 and dexamethasone was diminished by glucocorticoid responsive element (GRE) deletion and mutation or by an anti-glucocorticoid. These results indicated that FK506 causes the transcriptional induction of AGP, at least in part, via a glucocorticoid-mediated mechanism.
Shimoishi
K
K
Faculty of Pharmaceutical Sciences, Kumamoto University, 5-1 Oe-honmachi, 862-0973, Kumamoto, Japan.
Kai
H
H
Kabu
K
K
Komori
T
T
Maruyama
T
T
Otagiri
M
M
D000818:Animals; D015152:Blotting, Northern; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005786:Gene Expression Regulation / Q000187:drug effects; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008156:Luciferases / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D008297:Male; D009961:Orosomucoid / Q000235:genetics* / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011993:Recombinant Fusion Proteins / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D016559:Tacrolimus / Q000494:pharmacology*; D013997:Time Factors
D007166:Immunosuppressive Agents; D009961:Orosomucoid; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D003907:Dexamethasone; D008156:Luciferases; D016559:Tacrolimus