Antisense IRAK-1 oligonucleotide blocks activation of NF-kappa B and AP-1 induced by IL-18.

Interleukin-18 (IL-18) is a novel proinflammatory cytokine. Most of the immune and inflammatory genes induced by IL-18 are nuclear factor-kappaB (NF-kappaB)- and activator protein-1 (AP-1)-regulated. Interleukin-1 receptor-associated kinase-1 (IRAK-1) has recently been shown to be involved in IL-18-stimulated activation of NF-kappaB and AP-1. The purpose of this study is to investigate the effects of preventing IRAK-1 expression by antisense IRAK-1 oligodeoxynucleotide (ODN) on IL-18-stimulated activation of NF-kappaB and AP-1. Semiquantitative reverse transcription-PCR (RT-PCR) and western blot analysis revealed that antisense IRAK-1 ODN inhibited IRAK-1 mRNA and protein expression (P<0.01). As a result, antisense IRAK-1 ODN attenuated IL-18-induced activation of NF-kappaB and AP-1 as measured by sandwich ELISA in a concentration (1-8 microg ml(-1))- and time (5-24 h)-dependent fashion. These data suggest that antisense IRAK-1 ODN may share a role in the design of antiinflammatory therapeutics.