PMID- 10996021 OWN - NLM STAT- MEDLINE DCOM- 20010118 LR - 20190921 IS - 0162-3109 (Print) IS - 0162-3109 (Linking) VI - 49 IP - 3 DP - 2000 Sep TI - Antisense IRAK-1 oligonucleotide blocks activation of NF-kappa B and AP-1 induced by IL-18. PG - 241-6 AB - 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. FAU - Guo, F AU - Guo F AD - Institute of Pharmaceutic Sciences, The First Military Medical University, 510515, Guang Zhou, People's Republic of China. FAU - Wu, S AU - Wu S LA - eng PT - Journal Article PL - Netherlands TA - Immunopharmacology JT - Immunopharmacology JID - 7902474 RN - 0 (Enzyme Inhibitors) RN - 0 (Interleukin-18) RN - 0 (NF-kappa B) RN - 0 (Oligonucleotides, Antisense) RN - 0 (Protein Kinase Inhibitors) RN - 0 (Receptors, Interleukin-1) RN - 0 (Transcription Factor AP-1) RN - EC 2.7.- (Protein Kinases) RN - EC 2.7.11.1 (Interleukin-1 Receptor-Associated Kinases) SB - IM MH - Enzyme Activation/drug effects/genetics MH - Enzyme Inhibitors/pharmacology MH - Gene Expression Regulation/drug effects MH - Humans MH - Interleukin-1 Receptor-Associated Kinases MH - Interleukin-18/*antagonists & inhibitors/*physiology MH - NF-kappa B/*antagonists & inhibitors/genetics MH - Oligonucleotides, Antisense/*pharmacology MH - Protein Kinase Inhibitors MH - Protein Kinases/biosynthesis/*genetics/metabolism MH - Receptors, Interleukin-1/genetics/*metabolism MH - Transcription Factor AP-1/*antagonists & inhibitors/metabolism MH - Tumor Cells, Cultured EDAT- 2000/09/21 11:00 MHDA- 2001/02/28 10:01 CRDT- 2000/09/21 11:00 PHST- 2000/09/21 11:00 [pubmed] PHST- 2001/02/28 10:01 [medline] PHST- 2000/09/21 11:00 [entrez] AID - S0162310900002009 [pii] AID - 10.1016/s0162-3109(00)00200-9 [doi] PST - ppublish SO - Immunopharmacology. 2000 Sep;49(3):241-6. doi: 10.1016/s0162-3109(00)00200-9.