INTERLEUKIN-6 SIGNAL COMMUNICATION TO THE ALPHA-1-ACID GLYCOPROTEIN GENE, BUT NOT JUNB GENE, IS IMPAIRED IN HTC CELLS

In the rat hepatoma (HTC) cell line, transcription of the alpha1-acid glycoprotein (AGP) gene is prominently stimulated by dexamethasone. Al though interleukin (IL)-1 and IL-6 synergistically enhance expression of the AGP gene in liver, they have no detectable effect on this gene in HTC cells. Nevertheless, HTC cells have mRNA encoding the IL-6 rece ptor subunits and respond to IL-6 by increasing expression of the junB gene. The mRNA for the 80-kDa IL-6 receptors is increased severalfold following dexamethasone treatment. Even with elevated IL-6 receptor e xpression, no IL-6 regulation of the AGP gene is observed. The lack of response to IL-6 is also found with the transfected AGP gene sequence , suggesting the absence of specific trans-acting factors. Since IL-6 promotes only a minimal stimulation of the CCAAT/enhancer-binding prot ein beta, HTC cells lack the indirect IL-6 signaling pathway to acute phase plasma protein genes that has been found to be crucial in other hepatoma cell lines. Considering that a similar IL-6 regulation of the junB gene is manifested in HTC cells and normal liver, a separate IL- 6 signal-transducing pathway controlling the AGP gene is assumed to be missing in HTC cells.