Nuclear factors interacting with an interleukin-6 responsive element of rat α2-macroglobulin gene

Abstract

During acute inflammation, a group of liver-derived plasma proteins, acute phase proteins (APPs), increase in concentration. Interleukin-6 (IL-6) is responsible for this increase via the induction of APP gene expression. We have identified an IL-6 responsive cis-acting element (IL-6RE) of gene encoding a typical APP, rat α²-macroglobulin (α²M). The IL-6RE contains a sequence that is conserved among the 5′-flanking regions of various APP genes. Introduction of mutations into the conserved sequence revealed that the sequence, termed IL-6RE core, is a critical and essential component of IL6-RE. Nuclear factors binding to the IL-6RE core were identified in livers of normal and inflamed rats. Mobility shift pattern and DNase I footprinting profile indicated that the factors from normal and inflamed stages recognized the same sequence but were distinct from each other. These results suggested that the regulation of α₂M gene expression may involve mutually exclusive interaction of stage-specific trans-acting factors.