Effect of Anti-DNA Autoantibodies on the Gene Expression of Interleukin 8, Transforming Growth Factor-β, and Nitric Oxide Synthase in Cultured Endothelial Cells

Abstract

Our study aims to determine whether anti-dsDNA exerts any effect on the gene expression of IL-8 or TGF-β in cultured HUVEC. Both cytokines have angiogenic effect on endothelial cells. IgG was purified from 19 patients with SLE and from 19 healthy controls. Anti-dsDNA-depleted polyclonal IgG was also prepared from serum IgG of lupus patients by affinity chromatography with DNA cellulose column. Compared with either control IgG or anti-dsDNA-dep-IgG, HUVEC incubated with anti-dsDNA-containing-IgG expressed higher levels of IL-8 mRNA (p = 0.0001) and TGF-β1 mRNA (p = 0.0014). We demonstrated a significant increase in the percentage of cells with fragmented DNA in HUVEC incubated with anti-dsDNA-containing-IgG compared with those incubated with anti-dsDNA-dep-IgG, supporting the notion that anti-dsDNA may exert a direct apoptotic effect on cultured endothelial cells. Our study provides in vitro evidence that anti-dsDNA could play an important pathogenetic role in inducing inflammatory injury of vascular endothelium in SLE.

Key Words:

• Systemic lupus erythematosus
• anti-DNA autoantibodies
• endothelial cells
• interleukin 8
• transforming growth factor-β
• inducible nitric oxide synthase
• angiogenesis
• apoptosis