Constitutive and IL-6-induced nuclear factors that interact with the human C-reactive protein promoter

Transcription of the human C-reactive protein (CRP) gene is induced by interleukin-6 (IL-6) during acute inflammation. Important information for inducible CRP expression is located within the 90 bases preceding the transcriptional start site. We show that the CRP promoter contains two adjacent binding sites (β and α) that interact with at least two hepatocyte-specific nuclear protiens, H-APF-1 and H-APF-2. Point mutations that abolish or reduce binding drastically affect the level of CRP gene expression. Binding to β is identical when extracts from uninduced or IL-6-induced Hep3B cells are used. On the contrary, both quantitative and qualitative changes in the α binding can be detected with extracts from uninduced cells or from cells treated with IL-6 or IL-6 + cycloheximide. A synthetic promoter based on the multimerization of the β-binding domain, but not of the α-domain, is highly inducible when transfected in hepatoma cells. These results are discussed in relation to the structure of the promoter region of other acute phase inducible genes.