Molecular and cellular biology of serum amyloid A

Serum amyloid A (SAA) is one of the major acute-phase proteins in humans and mice. It is synthesized predominantly by the liver and secreted as a major component of the apolipoproteins in the high density lipoprotein particle. While the major physiological function of SAA is unclear, prolonged elevation of plasma SAA levels, as in chronic inflammation, however, results in the pathological condition amyloidosis affecting the liver, kidney and spleen. The expression of SAA mRNA is dramatically elevated in response to infection or systemic inflammation and is due primarily to the increased rate of SAA gene transcription. Studies in vitro and in vivo demonstrated that the expression of SAA genes is regulated by the inflammatory cytokine interleukin-1. Moreover, both the interleukin-1-induced expression and the enhanced liver-specific expression of the SAA gene are controlled by the binding of nuclear proteins to specific DNA sequences upstream from the structural gene.