NF kappa B decoy oligodeoxynucleotides reduce monocyte infiltration in renal allografts

Monocyte influx secondary to ischemia-reperfusion conditions the renal allograft to rejection by presentation of antigens and production of cytokines. Monocyte influx depends on NF kappa B-dependent transcription of genes encoding adhesion molecules and chemokines, Here we demonstrate that cationic liposomes containing phosphorothioated oligodeoxynucleotides (ODN) with the kappa B binding site serving as competitive binding decoy, can prevent TNF-alpha-induced NF kappa B activity in endothelial cells in vitro, In an allogenic rat kidney transplantation model (BN to LEW), we show that perfusing the renal allograft with this decoy prior to transplantation abolishes nuclear NF kappa B activity hi vivo and inhibits VCAM-1 expression in the donor endothelium (P