Nuclear factor κB decoy oligodeoxynucleotides prevent endotoxin-induced fatal liver failure in a murine model
Ichiro Ogushi
First Department of Surgery, Hyogo College of Medicine, Nishinomiya, Japan
Search for more papers by this authorYuji Iimuro
First Department of Surgery, Hyogo College of Medicine, Nishinomiya, Japan
Search for more papers by this authorEkihiro Seki
First Department of Surgery, Hyogo College of Medicine, Nishinomiya, Japan
Search for more papers by this authorGakuhei Son
First Department of Surgery, Hyogo College of Medicine, Nishinomiya, Japan
Search for more papers by this authorTadamichi Hirano
First Department of Surgery, Hyogo College of Medicine, Nishinomiya, Japan
Search for more papers by this authorToshikazu Hada
Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan
Search for more papers by this authorHiroko Tsutsui
Department of Immunology and Medical Zoology, Hyogo College of Medicine, Nishinomiya, Japan
Search for more papers by this authorKenji Nakanishi
Department of Immunology and Medical Zoology, Hyogo College of Medicine, Nishinomiya, Japan
Search for more papers by this authorRyuichi Morishita
Division of Gene Therapy Science, Graduate School of Medicine, Osaka University, Osaka, Japan
Search for more papers by this authorYasufumi Kaneda
Division of Gene Therapy Science, Graduate School of Medicine, Osaka University, Osaka, Japan
Search for more papers by this authorCorresponding Author
Jiro Fujimoto M.D.
First Department of Surgery, Hyogo College of Medicine, Nishinomiya, Japan
First Department of Surgery, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan. fax: (81) 798-45-6581===Search for more papers by this authorIchiro Ogushi
First Department of Surgery, Hyogo College of Medicine, Nishinomiya, Japan
Search for more papers by this authorYuji Iimuro
First Department of Surgery, Hyogo College of Medicine, Nishinomiya, Japan
Search for more papers by this authorEkihiro Seki
First Department of Surgery, Hyogo College of Medicine, Nishinomiya, Japan
Search for more papers by this authorGakuhei Son
First Department of Surgery, Hyogo College of Medicine, Nishinomiya, Japan
Search for more papers by this authorTadamichi Hirano
First Department of Surgery, Hyogo College of Medicine, Nishinomiya, Japan
Search for more papers by this authorToshikazu Hada
Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya, Japan
Search for more papers by this authorHiroko Tsutsui
Department of Immunology and Medical Zoology, Hyogo College of Medicine, Nishinomiya, Japan
Search for more papers by this authorKenji Nakanishi
Department of Immunology and Medical Zoology, Hyogo College of Medicine, Nishinomiya, Japan
Search for more papers by this authorRyuichi Morishita
Division of Gene Therapy Science, Graduate School of Medicine, Osaka University, Osaka, Japan
Search for more papers by this authorYasufumi Kaneda
Division of Gene Therapy Science, Graduate School of Medicine, Osaka University, Osaka, Japan
Search for more papers by this authorCorresponding Author
Jiro Fujimoto M.D.
First Department of Surgery, Hyogo College of Medicine, Nishinomiya, Japan
First Department of Surgery, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan. fax: (81) 798-45-6581===Search for more papers by this authorAbstract
Endotoxin syndrome is a systemic inflammatory response mediated by inflammatory cytokines. Nuclear factor κB (NF-κB) is the dominant regulator of the production of these cytokines by inflammatory cells. The aim of this study was to assess the efficacy of in vivo transfer of synthetic double-stranded oligodeoxynucleotides (ODN) with high affinity against NF-κB (NF-κB/decoy/ODN) as a therapeutic strategy for treating endotoxin-induced fatal liver injury. Liver injury was induced by administration of lipopolysaccharide (LPS) to Propionibacterium acnes-primed BALB/C mice. NF-κB/decoy/ODN was transferred into the portal vein using a fusigenic liposome with hemagglutinating virus of Japan. NF-κB/decoy/ODN was preferentially transferred to Kupffer cells, and activation of NF-κB after the LPS challenge was suppressed, leading to decreased inflammatory cytokine production. As a result, the massive necrosis and hepatocyte apoptosis observed in the control mice was dramatically attenuated and the survival rate improved. In conclusion, NF-κB/decoy/ODN transfer in vivo effectively suppressed endotoxin-induced fatal liver injury in mice.
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