IDENTIFICATION OF NOVEL INDUCIBLE NUCLEAR FACTORS THAT INTERACT WITH THE ACUTE PHASE RESPONSIVE PROMOTER ELEMENT OF RABBIT ALPHA-1-ACID GLYCOPROTEIN GENE

Alpha1-acid glycoprotein (α1-AGP) is a major acute phase protein that is highly inducible during hepatic acute-phase response. To identify the promoter element(s) required for increased gene transcription under acute condition a 529 bp 5′-flanking region of α1-AGP gene is fused to the chloramphenicol acetyl transferase (CAT) reporter gene and introduced into BNL liver cells. This DNA fragment is capable of inducing synthesis of the reporter gene-product about ten-fold when transfected cells are exposed to conditioned medium from lipopolysaccharide-stimulated peripheral monocytes. Deletion analyses have shown that sequences located between -224 to-22 are capable of eliciting this inducible promoter function. Using electromobility shift assay we have identified two novel inducible nuclear factors from turpentine-induced acute liver that can interact with this regulatory promoter region. Our results indicate that binding of these two factors to the promoter region of α1-AGP gene is highly specific in nature and the induction of this gene under acute condition may involve their participation. © 1992.