Anti-DNA autoantibodies stimulate the release of interleukin-1 and interleukin-6 from endothelial cells.
The pathogenetic mechanism of vasculitis in systemic lupus erythematosus (SLE) remains a subject of debate. Evidence for a direct pathogenetic role of anti-double-stranded DNA antibodies (anti-dsDNA) is not strong. Supernatant concentrations of interleukin-1 beta and interleukin-6, and mRNAs encoding for interleukin-1 alpha and interleukin-1 receptor-1 were determined in cultured human umbilical vein endothelial cells (HUVEC), incubated with control IgG (n = 18), anti-dsDNA (n = 18), or IgG from the same lupus patient depleted of anti-dsDNA by affinity chromatography (anti-dsDNA-dep-IgG). Compared with control IgG, there was a significant increase of supernatant interleukin-1 beta and interleukin-1 alpha mRNA in endothelial cells incubated with anti-dsDNA. The supernatant interleukin-1 beta and interleukin-6, and mRNAs encoding for interleukin-1 alpha and interleukin-1 receptor-1, were significantly elevated in endothelial cells incubated with anti-dsDNA, compared with those incubated with anti-dsDNA-dep-IgG. Pretreating HUVEC with native DNA before incubating with anti-dsDNA did not result in an additive effect. These in vitro studies suggest that anti-dsDNA plays an important pathogenetic role in inducing inflammatory injury of vascular endothelium in SLE.
Neng Lai
K
K
Department of Medicine, Chinese University of Hong Kong.
Leung
J C
JC
Bik Lai
K
K
Li
P K
PK
Lai
C K
CK
D000328:Adult; D000974:Antibodies, Antinuclear / Q000276:immunology*; D001483:Base Sequence; D018929:Cell Culture Techniques; D004247:DNA / Q000276:immunology*; D004730:Endothelium, Vascular / Q000276:immunology; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology; D007375:Interleukin-1 / Q000096:biosynthesis* / Q000235:genetics; D015850:Interleukin-6 / Q000096:biosynthesis*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008297:Male; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D017472:Receptors, Interleukin-1 / Q000235:genetics
D000974:Antibodies, Antinuclear; D007074:Immunoglobulin G; D007375:Interleukin-1; D015850:Interleukin-6; D012333:RNA, Messenger; D017472:Receptors, Interleukin-1; D004247:DNA