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To investigate whether interleukin-1 receptor-associated kinase-2 (IRAK-2) is involved in interleukin- 18 (IL- 18)-induced nuclear factor- κ B (NF- κ B) activation. Methods: Phosphorothioate oligodeoxynucleotide (ODN) was designed antisense to sequences of IRAK-2. Antisense IRAK-20DN was delivered by lipofectin encapsulation into cultured HepG2 cells. IRAK-2 mRNA expression was assayed by semiquantitative reverse transcription-PCR. The levels ofNF - κ B were measured by sandwich ELISA. Results: Antisense IRAK-20DN blocked IRAK -2 expression. IL-18 activated NF-κ B and the A value increased from a basal level of 0.115±0.004 to 2.141 ±0.038.Antisense IRAK-20DN inhibited IL-18-induced NF- κ B activation in a dose (1 - 8 μg )-dependent fashion. When the cells were treated with 4 μg antisense IRAK-20DN for 8 h, a maximum inhibition of 45.4% was induced as shown by the reduction of the OD valuefrom a control level of 2.141±0.038 down to 1.168±0.026. Conclusion: IRAK-2can regulate IL-18-stimulated NF-κ B activation.