EFFECTS OF INSULIN, DEXAMETHASONE AND CYTOKINES ON ALPHA(1)-ACID GLYCOPROTEIN GENE-EXPRESSION IN PRIMARY CULTURES OF NORMAL RAT HEPATOCYTES

While the effects of insulin, dexamethasone and cytokines on alpha(1)- acid glycoprotein gene expression have been investigated in various he patoma cell lines, the individual and combined effects of these compon ents on the expression of this gene have been rarely studied in cultur ed normal rat hepatocytes. In this cell model, we have shown that mRNA levels of alpha(1)-acid glycoprotein were not decreased at least duri ng the first 24 h of culture under basal conditions. During these shor t-term cultures, the expression of alpha(1)-acid glycoprotein in norma l hepatocytes showed a high degree of responsiveness to dexamethasone alone (20-fold increase) and to dexamethasone associated with various cytokines (interleukin-1 beta, interleukin-6 and tumor necrosis factor a) with a 40 to 100-fold increase depending on the cytokine. Insulin alone did not modify alpha(1)-acid glycoprotein mRNA; however, this ho rmone exerted a positive effect (about 50% increase) in the presence o f dexamethasone or dexamethasone with cytokines. These results indicat e that the regulation of alpha(1)-acid glycoprotein in cultured normal rat hepatocytes presents major differences when compared to reported observations in rat hepatoma cell lines.