Regulation of mouse serum amyloid P gene expression by cytokines in vitro

Inflammation is accompanied by an increase in the plasma levels of a number of proteins collectively known as acute-phase reactants (APRs). Serum amyloid P component (SAP) is a major mouse APR: hepatic SAP mRNA and plasma SAP protein concentrations increase by up to 20-fold in mice undergoing an inflammatory response. In-vitro studies, using primary hepatocyte cultures, have previously shown that SAP mRNA and protein levels increase in response to stimulation with a variety of cytokines such as monocyte-conditioned medium (MCM), interleukin 1 (IL-1), interleukin 6 (IL-6), tumor necrosis factor alpha (TNF-alpha) and transforming growth factor beta (TGF-beta). In this report, we have examined a mouse hepatoma cell line in which SAP gene regulation closely resembles that of primary hepatocytes. Accumulation of SAP mRNA in the +/+ Li mouse hepatoma cell line after stimulation with MCM, IL-1, IL-6 and the combination of IL-1 and IL-6 was demonstrated. This increase in the cellular content of SAP mRNA did not require new protein synthesis and was at least partially due to an increase in the transcription rate of the SAP gene.