INDUCTION OF SERUM AMYLOID-A (SAA) GENE BY SAA-ACTIVATING SEQUENCE-BINDING FACTOR (SAF) IN MONOCYTE MACROPHAGE CELLS - EVIDENCE FOR A FUNCTIONAL SYNERGY BETWEEN SAF AND SP1/

Serum amyloid A (SAA) is a plasma protein that is associated with many inflammatory diseases including amyloidosis, arthritis, and atheroscl erosis. SAA level is significantly increased during inflammatory condi tion, and such abnormal expression of this protein is linked to the pa thogenesis of the above-mentioned diseases, A promoter element, design ated as SAA-activating sequence (SAS), located between -280 and -226 h as been implicated in the induction mechanism and a nuclear factor, SA S-binding factor (SAF), has been shown to bind to this region, In this report, using a cloned SAF gene in transient transfection assay. we p rovide evidence that SAF potentiates SAA gene expression through SAS e lement. Furthermore, we show that during lipopolysaccharide-mediated i nduction of SAF, het eromeric complex with transcription factor Sp1 is formed, Transfection assays using both transcription factor genes hav e demonstrated that SAF-Sp1 heteromer is a highly potent transactivato r of SAA expression.