NFκB decoy delivery using dendritic poly(l-lysine) for treatment of endotoxin-induced hepatitis in mice

Yusuke Sugao, Kazuto Watanabe, Yuriko Higuchi, Ryohsuke Kurihara, Shigeru Kawakami, Mitsuru Hashida, Yoshiki Katayama, Takuro Niidome

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Mono-dispersed, 6th generation dendritic poly(l-lysine) (KG6) forms a stable complex with plasmid DNA and this complex can circulate in vivo for extended times before the DNA finally accumulates in the liver. In this study, we attempted to use KG6 as a carrier of NFκB decoy oligonucleotide to the liver to treat hepatitis, induced by lipopolysaccharide and d-galactosamine. KG6 formed a complex with the NFκB decoy. Serum aspartate aminotransferase and alanine aminotransferase were dramatically suppressed in the hepatitis mouse model after intravenous injection of KG6/NFκB decoy complexes. Expression levels of several cytokines and proteins related to the inflammatory reaction were also suppressed by intravenous administration of KG6/NFκB decoy complexes. Because [32P] NFκB decoy was found in non-parenchymal cells after intravenous injection, KG6 has been shown to be a promising carrier molecule of various oligonucleotides to non-parenchymal liver cells, including Kupffer cells.

Original languageEnglish
Pages (from-to)4990-4995
Number of pages6
JournalBioorganic and Medicinal Chemistry
Volume17
Issue number14
DOIs
Publication statusPublished - Jul 15 2009

Fingerprint

Endotoxins
Liver
Hepatitis
Lysine
Oligonucleotides
Intravenous Injections
Galactosamine
Kupffer Cells
DNA
Aspartate Aminotransferases
Alanine Transaminase
Intravenous Administration
Lipopolysaccharides
Plasmids
Therapeutics
Cytokines
Molecules
Serum
Proteins

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Cite this

Sugao, Y., Watanabe, K., Higuchi, Y., Kurihara, R., Kawakami, S., Hashida, M., ... Niidome, T. (2009). NFκB decoy delivery using dendritic poly(l-lysine) for treatment of endotoxin-induced hepatitis in mice. Bioorganic and Medicinal Chemistry, 17(14), 4990-4995. https://doi.org/10.1016/j.bmc.2009.05.081

NFκB decoy delivery using dendritic poly(l-lysine) for treatment of endotoxin-induced hepatitis in mice. / Sugao, Yusuke; Watanabe, Kazuto; Higuchi, Yuriko; Kurihara, Ryohsuke; Kawakami, Shigeru; Hashida, Mitsuru; Katayama, Yoshiki; Niidome, Takuro.

In: Bioorganic and Medicinal Chemistry, Vol. 17, No. 14, 15.07.2009, p. 4990-4995.

Research output: Contribution to journalArticle

Sugao, Y, Watanabe, K, Higuchi, Y, Kurihara, R, Kawakami, S, Hashida, M, Katayama, Y & Niidome, T 2009, 'NFκB decoy delivery using dendritic poly(l-lysine) for treatment of endotoxin-induced hepatitis in mice', Bioorganic and Medicinal Chemistry, vol. 17, no. 14, pp. 4990-4995. https://doi.org/10.1016/j.bmc.2009.05.081
Sugao, Yusuke ; Watanabe, Kazuto ; Higuchi, Yuriko ; Kurihara, Ryohsuke ; Kawakami, Shigeru ; Hashida, Mitsuru ; Katayama, Yoshiki ; Niidome, Takuro. / NFκB decoy delivery using dendritic poly(l-lysine) for treatment of endotoxin-induced hepatitis in mice. In: Bioorganic and Medicinal Chemistry. 2009 ; Vol. 17, No. 14. pp. 4990-4995.
@article{4021f8d22da94fdfb01bbdb8bbc78f08,
title = "NFκB decoy delivery using dendritic poly(l-lysine) for treatment of endotoxin-induced hepatitis in mice",
abstract = "Mono-dispersed, 6th generation dendritic poly(l-lysine) (KG6) forms a stable complex with plasmid DNA and this complex can circulate in vivo for extended times before the DNA finally accumulates in the liver. In this study, we attempted to use KG6 as a carrier of NFκB decoy oligonucleotide to the liver to treat hepatitis, induced by lipopolysaccharide and d-galactosamine. KG6 formed a complex with the NFκB decoy. Serum aspartate aminotransferase and alanine aminotransferase were dramatically suppressed in the hepatitis mouse model after intravenous injection of KG6/NFκB decoy complexes. Expression levels of several cytokines and proteins related to the inflammatory reaction were also suppressed by intravenous administration of KG6/NFκB decoy complexes. Because [32P] NFκB decoy was found in non-parenchymal cells after intravenous injection, KG6 has been shown to be a promising carrier molecule of various oligonucleotides to non-parenchymal liver cells, including Kupffer cells.",
author = "Yusuke Sugao and Kazuto Watanabe and Yuriko Higuchi and Ryohsuke Kurihara and Shigeru Kawakami and Mitsuru Hashida and Yoshiki Katayama and Takuro Niidome",
year = "2009",
month = "7",
day = "15",
doi = "10.1016/j.bmc.2009.05.081",
language = "English",
volume = "17",
pages = "4990--4995",
journal = "Bioorganic and Medicinal Chemistry",
issn = "0968-0896",
publisher = "Elsevier Limited",
number = "14",

}

TY - JOUR

T1 - NFκB decoy delivery using dendritic poly(l-lysine) for treatment of endotoxin-induced hepatitis in mice

AU - Sugao, Yusuke

AU - Watanabe, Kazuto

AU - Higuchi, Yuriko

AU - Kurihara, Ryohsuke

AU - Kawakami, Shigeru

AU - Hashida, Mitsuru

AU - Katayama, Yoshiki

AU - Niidome, Takuro

PY - 2009/7/15

Y1 - 2009/7/15

N2 - Mono-dispersed, 6th generation dendritic poly(l-lysine) (KG6) forms a stable complex with plasmid DNA and this complex can circulate in vivo for extended times before the DNA finally accumulates in the liver. In this study, we attempted to use KG6 as a carrier of NFκB decoy oligonucleotide to the liver to treat hepatitis, induced by lipopolysaccharide and d-galactosamine. KG6 formed a complex with the NFκB decoy. Serum aspartate aminotransferase and alanine aminotransferase were dramatically suppressed in the hepatitis mouse model after intravenous injection of KG6/NFκB decoy complexes. Expression levels of several cytokines and proteins related to the inflammatory reaction were also suppressed by intravenous administration of KG6/NFκB decoy complexes. Because [32P] NFκB decoy was found in non-parenchymal cells after intravenous injection, KG6 has been shown to be a promising carrier molecule of various oligonucleotides to non-parenchymal liver cells, including Kupffer cells.

AB - Mono-dispersed, 6th generation dendritic poly(l-lysine) (KG6) forms a stable complex with plasmid DNA and this complex can circulate in vivo for extended times before the DNA finally accumulates in the liver. In this study, we attempted to use KG6 as a carrier of NFκB decoy oligonucleotide to the liver to treat hepatitis, induced by lipopolysaccharide and d-galactosamine. KG6 formed a complex with the NFκB decoy. Serum aspartate aminotransferase and alanine aminotransferase were dramatically suppressed in the hepatitis mouse model after intravenous injection of KG6/NFκB decoy complexes. Expression levels of several cytokines and proteins related to the inflammatory reaction were also suppressed by intravenous administration of KG6/NFκB decoy complexes. Because [32P] NFκB decoy was found in non-parenchymal cells after intravenous injection, KG6 has been shown to be a promising carrier molecule of various oligonucleotides to non-parenchymal liver cells, including Kupffer cells.

UR - http://www.scopus.com/inward/record.url?scp=67650046793&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=67650046793&partnerID=8YFLogxK

U2 - 10.1016/j.bmc.2009.05.081

DO - 10.1016/j.bmc.2009.05.081

M3 - Article

VL - 17

SP - 4990

EP - 4995

JO - Bioorganic and Medicinal Chemistry

JF - Bioorganic and Medicinal Chemistry

SN - 0968-0896

IS - 14

ER -