登革病毒诱导人单核细胞miR-146a表达的机制研究

目的 探究登革病毒感染引起miR-146a高表达所依赖的天然免疫信号通路。方法 通过RNAi技术沉默登革病毒感染后激活的信号通路的上游蛋白,或采用信号分子抑制剂阻断登革病毒感染后激活的信号通路的下游因子,然后通过real-time PCR检测miR-146a的表达变化。 结果 DENV2感染引起的miR-146a的表达沉默IPS-1后减少了60%,而TLR3的沉默对miR-146a的表达无影响;采用特异性的抑制剂抑制NF-κB、IKK、p38和JNK后均可下调miR-146a的表达,而ERK的抑制对miR-146a的表达无明显影响。 结论 登革病毒感染诱导miR-146a的表达依赖于上游RIG-I/MDA5-IPS-1以及下游的p38、IKK/JNK和NF-κB,而不依赖于上游的TLR3和下游的ERK。miR-146a可能成为预防和治疗登革病毒感染的一个新靶标,最终为临床治疗和预防登革出血热提供一个新的视野。

Mechanism of dengue-virus-induced miR-146a expression in human monocytes

Objective To explore the innate immune signaling pathway that involved inhigh expression ofDENV2-induced miR-146a. Methods SiRNAs were used to silence upstream proteins of signaling pathway, molecule inhibitors were used to block downstream factors, and then real-time PCR was performed to detect the change in the expression of miR-146a.Results DENV2-induced miR-146a expression decreased by 60% in IPS-1-silencing cells, but not in TLR3-silencing cells. Furthermore, DENV2-induced miR-146a expression was reduced by using specific inhibitors of NF-κB, IKK, p38 and JNK, but not by ERK. Conclusions DENV2-induced miR-146a expression is dependent on RIG-I/MDA5-IPS-1, p38, JNK and IKK/NF-κB, but notdependent on TLR3in upstreamand ERK in downstream. miR-146a may become a new target for the prevention and treatment of dengue virus infection, and eventually provides a new perspective for clinical treatment and prevention of dengue hemorrhagic fever or dengue shock syndrome.