关键词: 白介素-1，白介素-1 受体相关激酶-1，反义寡核苷酸，核因子-κB

摘要：目的：研究反义白介素-1受体相关激酶-1(IRAK-1)寡核苷酸对核因子-κB(NF-κB)活化的影响。方法：Lipofectin介导反义IRAK-1寡核苷酸转染HepG2细胞，以逆转录PCR法检测IRAK-1mRNA表达水平，用SandwichELISA法检测NF-κB的活化。结果：反义IRAK-1寡核苷酸抑制IRAK-1mRNA表达；反义IRAK-1寡核苷酸呈剂量(1～8ug)和时间(5～24h)依赖性地抑制NF-κB活化，反义IRAK-1寡核苷酸4ug与细胞共孵育8h时抑制效果最好。结论：反义IRAK-1寡核苷酸通过阻断IRAK-1表达抑制NF-κB活化，预示反义IRAK-1寡核苷酸可潜在抑制IL-l的炎症活性。

Antisense IRAK-1 Oligonucleotide Blocking IL-l-stimulated NF-κB Activation

guo Fukun,Li Yilei,Wu Shuguang(Institute of Pharmaceutic Sciences,The First Military Medical University(Guangzhou 510515))

Abstract：To study the effects of antisense interleukin-1 receptor associated kinase-1 (IRAK-1)oligodeoxynucleotide (ODN) on IL-l-stimulated nuclear factor-κB (NF-κB) activation. Methods:Phosphorothioate ODN was designed to be antisense to sequences of IRAK-1.Antisense IRAK-1 ODN was delivered by lipofectin encapsulation into cultured HepG2 cells.The levels of IRAK-1 mRNA and NF-κB were measured by semiquantitative reverse transcription-PCR and sandwich ELISA,respectively.Results:Antisense IRAK-1 ODN blocked IRAK-1 mRNA expression.Antisense IRAK-1 ODN inhibited IL-l-induced NF-κB activation in a dose(1～8ug)-and time(5～24h)-dependent fashion.A maximum inhibition of NF-κB activation occurred when the cells were incubated with antisense IRAK-1 ODN 4ug for 8h.Conclusion:These data suggest that antisense IRAK-1 ODN may share a role in the design of antiinflammatory therapeutics.

Keywords：Interleukin-1,Interleukin-1 receptor associated kinase-1,Antisense oligodeoxynucleotide,NF-κB

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收稿日期：1999-07-26