CCAAT ENHANCER-BINDING PROTEIN-DELTA GENE-EXPRESSION IS MEDIATED BY APRF/STAT3/

The CCAAT/enhancer-binding protein delta (C/EBP delta) transcription f actor is known to be rarely expressed but sharply induced at an early stage of the acute phase response. To investigate the regulation mecha nisms for this induction, the 5'-flanking region of the rat C/EBP delt a gene was isolated. Functional analyses involving transfection and fo otprinting indicated that the upstream region up to -175 bp is suffici ent for the full basal activity in rat fibroblast 3Y1 cells. At least three cis-elements including a GC box are involved in this activity. W hen HepG2 cells were treated with interleukin-6 (IL-6), C/EBP delta mR NA was rapidly induced. Transfection and gel shift analyses identified the binding site for the acute phase response factor/signal transduce rs and activators of transcription (APRF/STAT3). These findings strong ly indicate that C/EBP delta gene expression is mediated by APRF/STAT3 , which is phosphorylated for the activation through the IL-6 receptor when cells are treated with IL-6, and trans-activates the other acute phase response genes.