EFFECT OF ANTI-DNA AUTOANTIBODIES ON THE GENE-EXPRESSION OF INTERLEUKIN-8, TRANSFORMING-GROWTH-FACTOR-BETA, AND NITRIC-OXIDE SYNTHASE IN CULTURED ENDOTHELIAL-CELLS

Our study aims to determine whether anti-dsDNA exerts any effect on th e gene expression of IL-8 or TGF-beta in cultured HUVEC. Both cytokine s have angiogenic effect on endothelial cells. IgG was purified from 1 9 patients with SLE and from 19 healthy controls. Anti-dsDNA-depleted polyclonal IgG was also prepared from serum IgG of lupus patients by a ffinity chromatography with DNA cellulose column. Compared with either control IgG or anti-dsDNA-dep-IgG, HUVEC incubated with anti-dsDNA-co ntaining-IgG expressed higher levels of IL-8 mRNA (p=0.0001) and TGF-b eta 1 mRNA (p=0.0014). We demonstrated a significant increase in the p ercentage of cells with fragmented DNA in HUVEC incubated with anti-ds DNA-containing-IgG compared with those incubated with anti-dsDNA-dep-I gG, supporting the notion that anti-dsDNA may exert a direct apoptotic effect on cultured endothelial cells. Our study provides in vitro evi dence that anti-dsDNA could play an important pathogenetic role in ind ucing inflammatory injury of vascular endothelium in SLE.