INVOLVEMENT OF AN SAF-LIKE TRANSCRIPTION FACTOR IN THE ACTIVATION OF SERUM AMYLOID-A GENE IN MONOCYTE MACROPHAGE CELLS BY LIPOPOLYSACCHARIDE/

Serum amyloid A (SAA) has been linked to atherosclerosis because of it s ability to remodel high-density lipoprotein by the depletion of apol ipoprotein Al, its ability to bind cholesterol, and its presence in th e atherosclerotic plaques of coronary and carotid arteries. Tn the pre sent study, we investigated the induction mechanism of SAA gene in THP -1 monocyte/macrophage cells which play a critical role in the develop ment of atherosclerotic fatty streak and plaque formation. We and othe rs have shown that SAA gene is induced in monocyte/macrophage cells by lipopolysaccharide (LPS). By promoter function analysis, we show that the SAA promoter sequence between -280 and -226 can confer LPS respon siveness. Gel electrophoretic mobility shift assay detected an induced DNA-binding activity in these cells in response to LPS. Characterizat ion of the DNA-binding protein by UV cross-linking, Southwestern blot, and antibody ablation/supershift assays revealed that it is similar t o a recently reported nuclear factor designated SAF. These results dem onstrated that LPS-mediated SAA gene induction in monocyte/macrophage cells is primarily due to the induction of SAF activity.