Fukushima J. Med. Sci.,
Vol. 53, No. 2, 2007

[Original Article]

INHIBITORY OLIGODEOXYNUCLEOTIDE IMPROVES
GLOMERULONEPHRITIS AND PROLONGS SURVIVAL
IN MRL-lpr/lpr MICE

NAMIKO HOSHI¹⁾, HIROSHI WATANABE¹⁾, HIROKO KOBAYASHI¹⁾,
HIDEHARU SEKINE¹⁾, NOBUO HOSHI²⁾, TAKASHI SUGINO²⁾,
TOSHIMITSU SUZUKI²⁾, YUKIO SATO³⁾ and HIROMASA OHIRA¹⁾

Departments of ¹⁾Internal Medicine II, ²⁾Pathology II and ³⁾Health Center, Fukushima Medical
University, Fukushima, 960-1295, Japan

(Received September 7, 2006, accepted October 1, 2007)

Abstract: 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.

Key words: MRL-lpr/lpr mouse, Systemic lupus erythematosus, Glomerulonephritis, Inhibitory oligodeoxynucleotides

星奈美子，渡辺浩志，小林浩子，関根英治，星　暢夫，杉野　隆，鈴木利光，佐藤由紀夫，大平弘正

Corresponding author: Namiko Hoshi
E-mail: pata@fmu.ac.jp