Inhibitory oligodeoxynucleotide improves glomerulonephritis and prolongs survival in MRL-lpr/lpr mice.
Inhibitory oligodeoxynucleotides (ODNs), which are capable of blocking CpG-induced inflammation, have been anticipated to be beneficial therapeutic agents for autoimmune diseases. In this study, we show that GpC ODN, which inverted the cytosine guanine sequence of CpG motif to guanine cytosine sequence, is an inhibitory ODN. The inhibitory effects of GpC ODN on CpG ODN-induced immune activation were confirmed by cytokine assay using splenocytes from lupus-prone MRL-lpr/lpr mice. In vivo, injecting MRL-lpr/lpr mice with GpC ODN did not reduce the deposition of IgG and C3 in the glomeruli, the serum level of IL-12, the serum level of rheumatoid factors and anti-ds DNA antibody, or alter the composition of IgG isotypes of anti-ds DNA antibody. However, the mice in the GpC group showed less proteinuria, significantly lower blood urea nitrogen levels (BUN) and significantly prolonged survival. Our results suggest that inhibitory ODNs, such as GpC ODN, have the potential to become a treatment for autoimmune diseases, like lupus nephritis.
Hoshi
Namiko
N
Department of Internal Medicine II, Fukushima Medical University, Fukushima, 960-1295, Japan. pata@fmu.ac.jp
Watanabe
Hiroshi
H
Kobayashi
Hiroko
H
Sekine
Hideharu
H
Hoshi
Nobuo
N
Sugino
Takashi
T
Suzuki
Toshimitsu
T
Sato
Yukio
Y
Ohira
Hiromasa
H
D000818:Animals; D001323:Autoantibodies / Q000097:blood; D001806:Blood Urea Nitrogen; D016207:Cytokines / Q000096:biosynthesis / Q000097:blood; D005260:Female; D005455:Fluorescent Antibody Technique; D005921:Glomerulonephritis / Q000188:drug therapy* / Q000276:immunology; D007668:Kidney / Q000473:pathology; D051379:Mice; D019463:Mice, Inbred MRL lpr; D009838:Oligodeoxyribonucleotides / Q000037:antagonists & inhibitors*; D011507:Proteinuria / Q000188:drug therapy
D001323:Autoantibodies; C408982:CPG-oligonucleotide; D016207:Cytokines; D009838:Oligodeoxyribonucleotides