title: Transfection of naked nuclear factor-κB decoy oligodeoxynucleotides into liver by rapid portal vein infusion in rats: its effect on ischemia-reperfusion injury of liver.
abstract: This study was aimed at examining whether rapid portal vein infusion (RPVI) of a small volume of naked oligodeoxynucleotides (ODNs) could be used to transfect sufficient amounts of nuclear factor-κB (NF-κB) decoy ODN into the liver to suppress NF-κB activation during liver ischemia-reperfusion (I/R) injury, in which NF-κB plays a central role in regulating the production of inflammatory cytokines. One milliliter of naked NF-κB decoy ODN solution was administered into the portal vein for a few seconds. Transfection efficacy was examined by labeling the ODN with a fluorescent tag. Activation of NF-κB was investigated by electrophoretic mobility shift assay. Levels of serum liver enzymes and cytokines were measured during liver I/R injury. NF-κB decoy ODN was preferentially incorporated into Kupffer cells and sinusoidal endothelial cells, but not hepatocytes, in the rat liver. Transfected NF-κB decoy ODN suppressed the function of NF-κB in both Kupffer cells and sinusoidal endothelial cells during liver I/R injury, causing significant decreases in serum tumor necrosis factor-α and interleukin-6 levels 3 hr after reperfusion. Although the decrease in serum liver enzymes was not significant, naked NF-κB decoy ODN was successfully incorporated into Kupffer cells and sinusoidal endothelial cells by rapid portal vein infusion, inhibited NF-κB activation in both cells, and suppressed the production of inflammatory cytokines during the early phase of liver I/R injury.
authors.affiliation: Department of Gastroenterological Surgery, Akita University Graduate School of Medicine, Akita 010-8543, Japan. gowata@med.akita-u.ac.jp
authors.forename: Go
authors.initials: G
authors.lastname: Watanabe
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Uchinami
authors.forename: Masato
authors.initials: M
authors.lastname: Yoshioka
authors.forename: Yuki
authors.initials: Y
authors.lastname: Abe
authors.forename: Isao
authors.initials: I
authors.lastname: Kikuchi
authors.forename: Wataru
authors.initials: W
authors.lastname: Iwasaki
authors.forename: Makoto
authors.initials: M
authors.lastname: Kume
authors.forename: Yuzo
authors.initials: Y
authors.lastname: Yamamoto
mesh_terms: D000818:Animals; D015316:Genetic Therapy; D007262:Infusions, Intravenous; D007728:Kupffer Cells / Q000378:metabolism; D008099:Liver / Q000098:blood supply / Q000473:pathology*; D008297:Male; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage* / Q000235:genetics*; D011169:Portal Vein; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D014162:Transfection
chemical_list: C468119:NF-kappaB decoy; D009838:Oligodeoxyribonucleotides