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 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.
Ray
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A
Department of Veterinary Pathobiology, University of Missouri, Columbia 65211, USA.
Ray
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BK
D000818:Animals; D001053:Apolipoproteins / Q000235:genetics*; D022762:CCAAT-Enhancer-Binding Proteins; D002467:Cell Nucleus / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008099:Liver / Q000378:metabolism*; D008297:Male; D016328:NF-kappa B / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D011485:Protein Binding; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D000685:Serum Amyloid A Protein / Q000235:genetics*; D014157:Transcription Factors / Q000378:metabolism*; D014425:Turpentine / Q000494:pharmacology
D001053:Apolipoproteins; D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009687:Nuclear Proteins; D012333:RNA, Messenger; D000685:Serum Amyloid A Protein; D014157:Transcription Factors; D014425:Turpentine