FK506 (tacrolimus) increases rat alpha(1)-acid glycoprotein expression in liver and primary cultured hepatocytes

FK506 (tacrolimus) (10 mg/kg. s.c., 5 days) increased rat alpha (1)-acid gl ycoprotein (AGP) in serum and AGP mRNA in liver. FK506 potentiated the dexa methasone-increased AGP expression in primary cultured hepatocytes. In the luciferase promoter assay. FK506 potentiated the dexamethasone-increased pr omoter activity of the AGP gene in cultured rat hepatocytes, although FK506 alone had no effect on its activity. The combined effect of FK506 and dexa methasone was diminished by glucocorticoid responsive element (GRE) deletio n and mutation or by an anti-glucocorticoid. These results indicated that F K506 causes the transcriptional induction of AGP, at least in part, via a g lucocorticoid-mediated mechanism. (C) 2001 Elsevier Science B.V. All rights reserved.