Regulation of synthesis of amyloid A-related protein.

The concentration of serum amyloid A polypeptide (SAAL) increases greatly during the acute phase responses to infection or inflammation. We find that SAAL synthesis comprises 2.5% of murine hepatic protein synthesis after lipopolysaccharide (LPS) administration, but much less in normal liver. SAAL messenger RNA (mRNA) in liver increases at least 500-fold above the normal level. A recombinant plasmid homologous to SAAL mRNA has been isolated, as has most of the mouse genome DNA encoding the plasmid's nucleotide sequence. This gene is transcribed into RNA much more frequently after LPS administration than it is in normal liver. In a number of other mammalian genes, cytosine methylation is inversely related to the rate of transcription. Methylation of CCGG sequences in hepatic DNA homologous to the recombinant plasmid has been examined. Little or no change is found after LPS administration. This suggests that other factors are responsible for the increase in SAAL mRNA in the acute phase response.