Transfection of NF-kappaB decoy oligodeoxynucleotides into macrophages reduces murine fatal liver failure after excessive hepatectomy.
BACKGROUND
Macrophages play an important role in the initiation of hypercytokinemia, which is involved in the development of liver failure after excessive hepatectomy. This study was aimed at evaluating whether the selective suppression of nuclear factor kappa B (NF-kappaB) in macrophages by decoy oligodeoxynucleotides (ODN) could prevent liver failure after excessive hepatectomy.


METHODS
Ninety percent hepatectomy was performed in 8-wk-old mice. NF-kappaB/decoy/ODN was transfected into the liver by the hemagglutinating virus of Japan-liposome method. The survival rate, serum levels of interleukin (IL)-1beta IL-6, and tumor necrosis factor-alpha, and the histological findings in the remnant liver were compared between the 90%-hepatectomized mice transfected with the decoy ODN (decoy group) and the 90%-hepatectomized mice injected with saline (control group).


RESULTS
The control group mice died within 48 h of the operation, while the survival rate in the decoy group at 48 h after the operation was 35%, and at 2 wk, 15%. The serum levels of all cytokines were significantly lower in the decoy group than in the control group. The number of terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling-positive cells in the remnant liver was smaller in the decoy group.


CONCLUSIONS
Transfection of NF-kappaB/decoy/ODN reduces fatal liver failure in mice after excessive hepatectomy by suppressing hypercytokinemia, but offers only a low rate of survival.
Takahashi
Takuji
T
Department of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Togo
Shinji
S
Kumamoto
Takafumi
T
Watanabe
Kazuteru
K
Kubota
Toru
T
Ichikawa
Yasushi
Y
Endo
Itaru
I
Kunisaki
Chikara
C
Nagashima
Yoji
Y
Fujimoto
Jiro
J
Shimada
Hiroshi
H
D000818:Animals; D017209:Apoptosis; D015316:Genetic Therapy / Q000379:methods*; D006498:Hepatectomy; D022781:Hepatocytes / Q000166:cytology; D015850:Interleukin-6 / Q000097:blood; D017093:Liver Failure / Q000276:immunology / Q000401:mortality / Q000517:prevention & control*; D008264:Macrophages / Q000502:physiology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016328:NF-kappa B / Q000235:genetics*; D009838:Oligodeoxyribonucleotides / Q000235:genetics; D011183:Postoperative Complications / Q000276:immunology / Q000401:mortality / Q000517:prevention & control*; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
D015850:Interleukin-6; D016328:NF-kappa B; D009838:Oligodeoxyribonucleotides; D014409:Tumor Necrosis Factor-alpha