Dexamethasone, but not IL-1 alone, upregulates acute-phase serum amyloid Agene expression and production by cultured human aortic smooth muscle cells

Although the SAA1 and SAA2 protein isoforms (A-SAA) of the serum amyloid A (SAA) family of acute phase reactants have been found in a number of extrah epatic tissues; the site of synthesis of extrahepatic SAA remains to be cla rified. To investigate site(s) of synthesis of the SAA protein localized to atherosclerotic plaque, expression of the SAA1 and SAA2 genes by cultured human aortic smooth muscle cells (HASMC) was investigated, A-SAA protein is oforms were detectable by immunoblot analysis in the culture medium of HASM C. Both A-SAA and C-SAA (SAA4) mRNA isoforms were constitutively expressed by HASMC, but not, however, by the human umbilical vein endothelial cells. Expression of A-SAA mRNA by HASMC was upregulated by corticoid hormones inc luding dexamethasone (Dex), corticosterone, hydrocortisone, and aldosterone , but not by the cytokines interleukin (IL)-1, IL-6, and tumour necrosis fa ctor (TNF)-alpha alone. Dex stimulation of A-SAA mRNA was time and dose dep endent from 6 to 48 h. The threshold concentration for upregulation of A-SA A mRNA in HASMC by Dex was between 0.1 and 1 nM. IL-1, known to upregulate extrahepatic A-SAA gene expression in other cell systems only slightly, if at all, upregulated Dex-induced A-SAA expression by HASMC. Thus, it is poss ible that some of the A-SAA protein in the vascular wall (atherosclerotic p laques) can originate from smooth muscle cells. In consideration of recent reports that A-SAA modulates the inflammatory process and lipid synthesis, A-SAA can potentially serve as a physiological regulator of smooth muscle c ell homeostasis within that, in a disease state, participates in the format ion of atherosclerotic plaques.