sIL-6R调控TRAF6/NFκB信号通路在IAV诱导的细胞因子风暴中的作用及机制

Highly pathogenic influenza A virus infection induced acute lung injury (ALI) is a serious disease, the key treatment is to carry out early prevention and treatment. The production of cytokine storm in lung is considered to be the key link of ALI. Based on the previous work, we found that the soluble interleukin-6 receptor (sIL-6R) may play an important role in the influenza virus-induced cytokine storm and screened with sIL-6R interacting protein - TRAF6 by Yeast two - hybrid experiment. Through in vivo and in vitro assay, Co-immunoprecipitation (Co-IP) assay, Glutathione-S-transferase (GST)-Pull Down assay, and confocal immunofluorescence, this grant try to identify the fact that sIL-6R regulates cytokine storm induced by influenza A virus. Further, we will demonstrate the mechanism of sIL-6R triggers NFκB signal pathway through interaction with TRAF6 and activates TRAF6 compound related proteins(IRAK1、IRAK4), induces expression of inflammatory factors, then promotes cytokine storm, and ultimately provide new information and strategies for the development of anti-infective drugs and early prevention and treatment of acute lung injury.

高致病性甲型流感病毒感染诱发的急性肺损伤(ALI)属于危重症疾病,能否开展早期防治已成为救治的关键。肺内细胞因子风暴的产生被认为是ALI发生发展的关键环节。在前期研究工作基础上, 我们发现可溶性白细胞介素6受体(sIL-6R)可能在甲流病毒感染诱导的细胞因子风暴中发挥重要作用，并经酵母双杂交实验筛选出与sIL-6R相互作用蛋白——TRAF6。本项目拟开展体内及体外实验、Co-IP、GST-Pull Down、激光共聚焦等,力图明确sIL-6R参与甲流病毒诱导的细胞因子风暴产生,阐述sIL-6R通过与TRAF6相互作用,启动NFκB信号通路,激活TRAF6复合物相关蛋白 (IRAK1、IRAK4),诱导炎症因子表达,促进细胞因子风暴发生的机制,并最终为抗感染药物的研发及早期防治急性肺损伤提供新的信息和策略。