Regulation of Amyloid A Gene Expression in Cultured Cells

Abstract

Serum amyloid A (SAA) proteins are secreted by mammalian liver in response to inflammatory stimuli. Both transcriptional and posttranscriptional mechanisms have been shown to regulate the 2,000-fold increase in SAA mRNA after injection of endotoxin into mice. We report here the characterization of a cell line derived from mouse liver (BNL) in which the expression of SAA3 mRNA is regulated. In this model, SAA3 mRNA accumulated in response to conditioned medium from the mouse macrophage P388D1 cell line with kinetics similar to that seen in mouse liver (C. A. Lowell, R. S. Stearman, and J. F. Morrow, J. Biol. Chem. 261:8453-8461, 1986). In in vitro nuclear transcription assays, the SAA3 gene was transcribed equally in induced and uninduced cells. In addition, in steady-state RNA studies treatment with conditioned medium allowed the cells to rapidly accumulate SAA3 mRNA without an apparent change in half-life. These observations suggest that conditioned medium contains a factor(s) that acts directly on hepatocytes to regulate SAA3 mRNA processing.