SERUM AMYLOID-A GENE-EXPRESSION LEVEL IN LIVER IN RESPONSE TO DIFFERENT INFLAMMATORY AGENTS IS DEPENDENT UPON THE NATURE OF ACTIVATED TRANSCRIPTION FACTORS

Serum amyloid A (SAA) is highly induced during many inflammatory episo des, The induction mechanism in response to turpentine and lipopolysac charide (LPS), two major inducers of this gene, was investigated. Here we present evidence that although both agents triggered expression, S AA mRNA synthesized in the turpentine-injected rabbit liver is many-fo ld higher compared to that found in LPS-injected rabbit liver, We demo nstrate that differential level of activation of C/EBP and NF-kappa B that interact with the proximal promoter of SAA gene is responsible fo r the differential expression, A very high level of C/EBP induction wi th little or no activation of NF-kappa B factors was noted when turpen tine was used as the inducer, LPS, on the other hand, activated NF-kap pa B and C/EBP, which were detected only at the early phase of inducti on process, These results indicate that different pathways might be ac tivated for the regulation of hepatic expression of SAA by different i nflammatory agents, One of the pathways, triggered by LPS, requires pa rticipation of both NF-kappa B and C/EBP, A second pathway, triggered by turpentine, involves only C/EBP family of transcription factors.