A SAF binding site in the promoter region of human gamma-fibrinogen gene functions as an IL-6 response element.

Expression of fibrinogen is highly induced during inflammation, and such abnormal expression of this protein is considered as a major cardiovascular risk factor. IL-6 is one of the main mediators of abnormal expression of fibrinogen leading to the pathogenic conditions. Transient transfection and EMSA were performed to investigate the molecular mechanism of IL-6-induced gamma-fibrinogen gene expression in hepatic cells. Using progressively deleted 5' fragments of the gamma-fibrinogen promoter coupled to chloramphenicol acetyltransferase gene, an IL-6 responsive element located between positions -273 and -259 was identified. Mutation of this element abrogates IL-6 responsiveness of the gamma-fibrinogen promoter. Interaction of this promoter with a zinc finger transcription factor, serum amyloid A activating factor (SAF)-1, was demonstrated by EMSA. Furthermore, overexpression of wild-type SAF-1 in transfected liver cells can increase transcription of the gamma-fibrinogen promoter. These data show that transcription factor SAF-1 is involved in the regulation of IL-6-mediated induction of the human gamma-fibrinogen gene in liver cells.