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.
Guo
F
F
Institute of Pharmaceutic Sciences, The First Military Medical University, 510515, Guang Zhou, People's Republic of China.
Wu
S
S
D004789:Enzyme Activation / Q000187:drug effects / Q000235:genetics; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D053592:Interleukin-1 Receptor-Associated Kinases; D020382:Interleukin-18 / Q000037:antagonists & inhibitors* / Q000502:physiology*; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000235:genetics; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D017472:Receptors, Interleukin-1 / Q000235:genetics / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014407:Tumor Cells, Cultured
D004791:Enzyme Inhibitors; D020382:Interleukin-18; D016328:NF-kappa B; D016376:Oligonucleotides, Antisense; D047428:Protein Kinase Inhibitors; D017472:Receptors, Interleukin-1; D018808:Transcription Factor AP-1; D011494:Protein Kinases; D053592:Interleukin-1 Receptor-Associated Kinases