A double-strand decoy DNA oligomer for NF-kappaB inhibits TNFalpha-induced ICAM-1 expression in sinusoidal endothelial cells.
Altered gene expression of liver sinusoidal endothelial cells (SECs) is associated with impaired immune response. Here we report that the decoy technique effectively suppresses TNFalpha-induced ICAM-1 expression in SEC. An NF-kappaB decoy (NF-kappaB31: 5(')-TGGGGACTTTCCAGTTTCTGGAAAGTCCCCA-3), which contains a consensus sequence for NF-kappaB, was complexed to PLL-g-HA [hyaluronate-grafted poly(L-lysine) copolymer] that permits transfer of exogenous DNA selectively to the SEC. The PLL-g-HA/NF-kappaB31 complex was added to the culture media of LSE cells, a human SEC-derived cell line. Then, cells were stimulated with TNFalpha (5ng/mL). PLL-g-HA/NF-kappaB31, but not control oligodeoxynucleotides having a reverse or scrambled sequence, inhibited the intranuclear localization of NF-kappaB induced by TNFalpha, with almost complete inhibition at 2.5microg/mL as DNA. NF-kappaB31 attenuated the increase in ICAM-1 mRNA as well as protein levels in LSE cells. The decoy technique in combination with PLL-g-HA may provide a novel strategy for manipulation of SEC functions.
Shibuya
Tomoyoshi
T
Department of Gastroenterology, Juntendo University School of Medicine, 2-1-1 Hongo, Bunkyo-ku, 113-8421, Tokyo, Japan.
Takei
Yoshiyuki
Y
Hirose
Miyoko
M
Ikejima
Kenichi
K
Enomoto
Nobuyuki
N
Maruyama
Atsushi
A
Sato
Nobuhiro
N
D021581:Active Transport, Cell Nucleus; D001483:Base Sequence; D001704:Biopolymers / Q000494:pharmacology; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D016384:Consensus Sequence; D004730:Endothelium, Vascular / Q000378:metabolism*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis* / Q000235:genetics; D008099:Liver / Q000166:cytology*; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009838:Oligodeoxyribonucleotides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015854:Up-Regulation
D001704:Biopolymers; D016328:NF-kappa B; C468119:NF-kappaB decoy; D009838:Oligodeoxyribonucleotides; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1