REGULATION OF EXTRAHEPATIC APOLIPOPROTEIN SERUM AMYLOID A (APOSAA) GENE-EXPRESSION BY INTERLEUKIN-1-ALPHA ALONE - SYNTHESIS AND SECRETION OF APOSAA BY CULTURED AORTIC SMOOTH-MUSCLE CELLS

Serum amyloid A apolipoproteins (apoSAA) appear to compromise the abil ity of high density lipoprotein to protect against atherosclerosis and it is of interest to determine whether aortic smooth muscle cells can contribute to local pools of apoSAA in the presence of cytokines that are known to stimulate acute phase apoSAA (A-apoSAA) synthesis in the liver, In this study, the regulation of A-apoSAA synthesis was monito red in cultured neonatal rabbit aortic smooth muscle cells, Constituti ve apoSAA(3) gene expression was minimal, and only detectable by ampli fication of the mRNA by reverse transcriptase-polymerase chain reactio n. ApoSAA(3) gene expression and protein synthesis were stimulated by IL-1 alpha: as little as 0.01 ng/ml of IL-1 alpha stimulated an increa se in steady state levels of apoSAA(3) mRNA. Interestingly, IL-6 (whic h is required in addition to IL-1 alpha for the optimal synthesis of A -apoSAA by human hepatoma cells) had little if any effect on apoSAA(3) synthesis by the smooth muscle cells. In a time course, it was shown that the stimulation of apoSAA(3) mRNA levels was apparent by 1-2h aft er the addition of cytokine, and that levels remained elevated in the presence of the cytokine for at least 48h. Immunoprecipitation using a n antiserum directed against apoSAA(3) revealed that IL-1 alpha stimul ated the synthesis and secretion of apoSAA3 protein in a manner that w as consistent with apoSAA(3) mRNA expression, The implications of thes e findings in atherogenesis are discussed.