Identification of novel inducible nuclear factors that interact with the acute phase responsive promoter element of rabbit alpha 1-acid glycoprotein gene.
Alpha 1-acid glycoprotein (alpha 1-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 alpha 1-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 alpha 1-AGP gene is highly specific in nature and the induction of this gene under acute condition may involve their participation.