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Nuclear factor κB decoy oligodeoxynucleotides prevent endotoxin‐induced fatal liver failure in a murine model
Author(s) -
Ogushi Ichiro,
Iimuro Yuji,
Seki Ekihiro,
Son Gakuhei,
Hirano Tadamichi,
Hada Toshikazu,
Tsutsui Hiroko,
Nakanishi Kenji,
Morishita Ryuichi,
Kaneda Yasufumi,
Fujimoto Jiro
Publication year - 2003
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1053/jhep.2003.50298
Subject(s) - decoy , in vivo , lipopolysaccharide , medicine , cytokine , nfkb1 , apoptosis , tumor necrosis factor alpha , liver injury , proinflammatory cytokine , immunology , pharmacology , inflammation , chemistry , biology , receptor , biochemistry , microbiology and biotechnology , gene , transcription factor
Abstract 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.