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 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.
Lai
K N
KN
Department of Medicine, Queen Mary Hospital, University of Hong Kong, Hong Kong.
Leung
J C
JC
Lai
K B
KB
Lai
C K
CK
D000328:Adult; D000974:Antibodies, Antinuclear / Q000494:pharmacology*; D017209:Apoptosis / Q000276:immunology; D002478:Cells, Cultured; D004247:DNA / Q000276:immunology*; D053938:DNA Fragmentation; D004730:Endothelium, Vascular / Q000166:cytology / Q000201:enzymology / Q000276:immunology; D005260:Female; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000494:pharmacology; D016209:Interleukin-8 / Q000235:genetics*; D008180:Lupus Erythematosus, Systemic / Q000276:immunology; D008297:Male; D019001:Nitric Oxide Synthase / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D016212:Transforming Growth Factor beta / Q000235:genetics*; D014471:Umbilical Veins / Q000166:cytology
D000974:Antibodies, Antinuclear; D007074:Immunoglobulin G; D016209:Interleukin-8; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D004247:DNA; D019001:Nitric Oxide Synthase