Ray A, Ray B K
Department of Veterinary Pathobiology, University of Missouri, Columbia 65211, USA.
DNA Cell Biol. 1997 Jan;16(1):1-7. doi: 10.1089/dna.1997.16.1.
Serum amyloid A (SAA) is highly induced during many inflammatory episodes. The induction mechanism in response to turpentine and lipopolysaccharide (LPS), two major inducers of this gene, was investigated. Here we present evidence that although both agents triggered expression, SAA mRNA synthesized in the turpentine-injected rabbit liver is many-fold higher compared to that found in LPS-injected rabbit liver. We demonstrate that differential level of activation of C/EBP and NF-kappaB that interact with the proximal promoter of SAA gene is responsible for the differential expression. A very high level of C/EBP induction with little or no activation of NF-kappaB factors was noted when turpentine was used as the inducer. LPS, on the other hand, activated NF-kappaB and C/EBP, which were detected only at the early phase of induction process. These results indicate that different pathways might be activated for the regulation of hepatic expression of SAA by different inflammatory agents. One of the pathways, triggered by LPS, requires participation of both NF-kappaB and C/EBP. A second pathway, triggered by turpentine, involves only C/EBP family of transcription factors.
血清淀粉样蛋白A（SAA）在许多炎症发作期间会被高度诱导。我们研究了该基因的两种主要诱导剂——松节油和脂多糖（LPS）的诱导机制。在此我们提供证据表明，尽管这两种试剂都能触发表达，但在注射松节油的兔肝脏中合成的SAA mRNA比注射LPS的兔肝脏中的SAA mRNA高出许多倍。我们证明，与SAA基因近端启动子相互作用的C/EBP和NF-κB的不同激活水平是差异表达的原因。当使用松节油作为诱导剂时，观察到C/EBP诱导水平非常高，而NF-κB因子几乎没有激活或没有激活。另一方面，LPS激活了NF-κB和C/EBP，它们仅在诱导过程的早期阶段被检测到。这些结果表明，不同的炎症因子可能通过不同的途径激活来调节肝脏中SAA的表达。由LPS触发的其中一条途径需要NF-κB和C/EBP的参与。由松节油触发的第二条途径仅涉及C/EBP转录因子家族。
