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目的研究含阻遏蛋白结构域蛋白4(arrestin domain-containing protein 4,ARRDC4)对肠道病毒71(EV71)诱导IL-6产生的调节作用和相关机制。方法利用特异性靶向ARRDC4的小干扰RNA(siRNA)在THP-1诱导分化的巨噬细胞(t-M_φ)中干扰ARRDC4的表达,无关siRNA序列干扰作为阴性对照组,采用实时定量PCR、ELISA和Western印迹等技术观察ARRDC4对IL-6产生、EV71复制以及相关天然免疫信号通路接头分子活化的影响。结果 EV71感染时,ARRDC4表达显著上调。以siRNA靶向干扰ARRDC4的表达,能抑制EV71感染诱导的IL-6 mRNA的表达和IL-6的分泌产生,促进EV71的复制。靶向干扰ARRDC4能明显抑制EV71诱导的p-65、IκBα、ERK、JNK和p38的活化。结论 ARRDC4通过增强NF-κB和MAPK信号通路的活化,促进EV71诱导的IL-6产生,从而抑制EV71的复制,正向调控EV71触发的天然免疫反应。
Objective To investigate the regulatory effect of arrestin domain-containing protein 4 (ARRDC4) on IL-6 induced by enterovirus 71 (EV71) and its related mechanisms. Methods siRNA targeting ARRDC4 was used to interfere the expression of ARRDC4 in THP-1-induced macrophages (t-M_φ). Negative siRNA sequences were used as negative control. Real-time PCR and ELISA And Western blotting were used to observe the effect of ARRDC4 on IL-6 production, EV71 replication and activation of the innate immune signaling pathway linker molecules. The results of EV71 infection, ARRDC4 expression was significantly increased. Targeting siRNA to interfere with the expression of ARRDC4 can inhibit the expression of IL-6 mRNA and IL-6 secreted by EV71 infection and promote the replication of EV71. Targeted interference with ARRDC4 significantly inhibited EV71-induced activation of p-65, IκBα, ERK, JNK and p38. Conclusion ARRDC4 can enhance the activation of NF-κB and MAPK signaling pathway and promote EV71-induced IL-6 production, thus inhibiting the replication of EV71 and positively regulating the innate immune response triggered by EV71.