Transcriptional complex formation of c-Fos, STAT3, and hepatocyte NF-1 alpha is essential for cytokine-driven C-reactive protein gene expression.

C-reactive protein (CRP) is a sensitive marker and mediator of inflammation, whereas IL-6 blocking therapy can normalize serum levels of CRP in chronic inflammatory diseases. We investigated the precise synergistic induction mechanism of CRP gene expression by IL-1 and IL-6 in Hep3B cells. In the early induction phase, IL-1 inhibited IL-6-mediated CRP gene expression, and NF-kappaB p65 inhibited the luciferase activity of pGL3-CRP by IL-1 plus IL-6 even in the presence of overexpressed STAT3.