Effect of anti-DNA autoantibodies on the gene expression of interleukin 8, transforming growth factor-beta, and nitric oxide synthase in cultured endothelial cells

Scand J Rheumatol. 1997;26(6):461-7. doi: 10.3109/03009749709065720.

Abstract

Our study aims to determine whether anti-dsDNA exerts any effect on the gene expression of IL-8 or TGF-beta 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-beta 1 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antibodies, Antinuclear / pharmacology*
  • Apoptosis / immunology
  • Cells, Cultured
  • DNA / immunology*
  • DNA Fragmentation
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / enzymology
  • Endothelium, Vascular / immunology
  • Female
  • Flow Cytometry
  • Gene Expression Regulation / immunology
  • Humans
  • Immunoglobulin G / pharmacology
  • Interleukin-8 / genetics*
  • Lupus Erythematosus, Systemic / immunology
  • Male
  • Nitric Oxide Synthase / genetics*
  • RNA, Messenger / analysis
  • Transforming Growth Factor beta / genetics*
  • Umbilical Veins / cytology

Substances

  • Antibodies, Antinuclear
  • Immunoglobulin G
  • Interleukin-8
  • RNA, Messenger
  • Transforming Growth Factor beta
  • DNA
  • Nitric Oxide Synthase