CONCERTED PARTICIPATION OF NF-KB AND C EBP HETEROMER IN LIPOPOLYSACCHARIDE INDUCTION OF SERUM AMYLOID A GENE-EXPRESSION IN LIVER/

The promoter region of the rabbit serum amyloid A (SAA) gene contains two adjacent C/EBP and one NF-kappa B binding element. Involvement of these elements in SAA gene induction, following lipopolysaccharide (LP S) stimulation of the liver, has been studied by investigating LPS-act ivated transcription factors and their interaction with the promoter e lements of the SAA gene. Appearance of complexes in the electrophoreti c mobility shift assay has indicated that DNA-binding proteins that in teract with the NF-KB element of the SAA promoter are induced in the L PS-treated rabbit liver. Presence of RelA (p65 subunit of NF-kappa B) in these complexes was demonstrated by the ability of RelA-specific an tisera to supershift the DNA-protein complexes. LPS also induced sever al members of the C/EBP family of transcription factors, which interac ted with the C/EBP motifs of the SAA promoter. Activated C/EBP and Rel A form a RelA . C/EBP heteromeric complex that associates with varying affinity to NF-kappa B and C/EBP elements of the SAA gene. Transfecti on assays using both transcription factor genes have demonstrated that the hetero complex of NF-kappa B and C/EBP is a much more potent tran sactivator of SAA expression than each transcription factor alone. The heteromeric complex efficiently promotes transcription from both NF-k appa B and C/EBP sites.