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'-TGGGGACTTTCCAGTTTCTGGAAAG TCCCCA-3), which contains a consensus sequence for NF-kappaB, was complexed to PLL-g-HA [hyaluronate-grafted poly(t-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 (5 ng/mL). PLL-g-HA/NF-kappaB31, but not control oligodcoxynucleotides having a reverse or scrambled sequence. inhibited the intranuclear localization of NF-kappaB induced by TNFalpha, with almost complete inhibition at 2.5 mug/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. (C) 2002 Elsevier Science (USA). All rights reserved.