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-Fibrinogen Gene Functions as an IL-6 Response Element 1
Department of Veterinary Pathobiology, University of Missouri, Columbia, MO 65211
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 
-fibrinogen gene expression in
hepatic cells. Using progressively deleted 5' fragments of the
-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 -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 -fibrinogen promoter. These data show
that transcription factor SAF-1 is involved in the regulation of
IL-6-mediated induction of the human -fibrinogen gene in liver
cells.
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