Antisense IRAK-2 oligonucleotide blocks IL-1-stimulated NF-kappaB activation and ICAM-1 expression in cultured endothelial cells.

Phosphorothioate oligodeoxynucleotide (ODN) was designed antisense to sequences of the recently cloned human IL-1 receptor associated kinase-2 (IRAK-2). Antisense IRAK-2 ODN was delivered by lipofectin encapsulation into cultured endothelial cells. The levels of NF-KB, surface expression of intracellular adhesion molecule-1 (ICAM-1), ICAM-1 and IRAK-2 mRNAs were measured by sandwich ELISA, ELISA on cells in situ, and semiquantitative reverse transcription-PCR (RT-PCR), respectively. Antisense IRAK-2 ODN inhibited IL-1-induced NF-KB activation and surface expression of ICAM-1 in a concentration (1-4 microg)- and time (5-24 h)-dependent fashion. A maximum inhibition of NF-KB activation or surface expression of ICAM-1 occurred when the cells were incubated with antisense IRAK-2 ODN 3 microg for 8 h. IL-1-induced ICAM-1 mRNA expression was also inhibited after treatment of cells with antisense IRAK-2 ODN 3 microg for 8 h. The attenuation of the cellular response to IL-1 caused by antisense IRAK-2 ODN correlated with a reduction of IRAK-2 expression. These data suggest that antisense IRAK-2 ODN may share a role in the design of antiinflammatory therapeutics.