title: NFkappaB 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 NFkappaB decoy oligonucleotide to the liver to treat hepatitis, induced by lipopolysaccharide and d-galactosamine. KG6 formed a complex with the NFkappaB decoy. Serum aspartate aminotransferase and alanine aminotransferase were dramatically suppressed in the hepatitis mouse model after intravenous injection of KG6/NFkappaB decoy complexes. Expression levels of several cytokines and proteins related to the inflammatory reaction were also suppressed by intravenous administration of KG6/NFkappaB decoy complexes. Because [(32)P] NFkappaB 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.
authors.affiliation: Department of Applied Chemistry, Faculty of Engineering, Kyushu University, 744 Motooka, Nishi-ku, Fukuoka 819-0395, Japan.
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Sugao
authors.forename: Kazuto
authors.initials: K
authors.lastname: Watanabe
authors.forename: Yuriko
authors.initials: Y
authors.lastname: Higuchi
authors.forename: Ryohsuke
authors.initials: R
authors.lastname: Kurihara
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kawakami
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Hashida
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Katayama
authors.forename: Takuro
authors.initials: T
authors.lastname: Niidome
mesh_terms: D000818:Animals; D001483:Base Sequence; D056486:Chemical and Drug Induced Liver Injury / Q000188:drug therapy*; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D050091:Dendrimers / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D005688:Galactosamine; D008070:Lipopolysaccharides; D008099:Liver / Q000166:cytology; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000235:genetics*; D009841:Oligonucleotides / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011107:Polylysine / Q000737:chemistry*; D012333:RNA, Messenger / Q000235:genetics; D000637:Transaminases / Q000097:blood / Q000378:metabolism
chemical_list: D016207:Cytokines; D050091:Dendrimers; D004337:Drug Carriers; D008070:Lipopolysaccharides; D016328:NF-kappa B; D009841:Oligonucleotides; D012333:RNA, Messenger; D011107:Polylysine; D005688:Galactosamine; D000637:Transaminases