肺内皮细胞S1PR1受体在流感病毒所致ARDS中的作用

项目名称： 肺内皮细胞S1PR1受体在流感病毒所致ARDS中的作用

项目编号： No.81470206

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 施毅

作者单位： 中国人民解放军东部战区总医院

项目金额： 75万元

中文摘要： 炎症反应引发的ARDS是流感患者死亡的首要原因，最新研究证实肺内皮细胞是流感所致炎症反应的枢纽环节，激动其S1PR1受体可显著降低炎症程度。目前，参与流感炎症反应的肺内皮细胞类型仍不清楚，且S1PR1受体调控肺内皮细胞促炎因子产生的机制不明。本课题前期研究证实甲型H1N1病毒感染人血管内皮细胞后可诱导促炎因子产生及细胞凋亡，S1PR1特异性激动剂可抑制促炎因子产生。据此我们认为：血管内皮细胞参与流感病毒感染后炎症反应，激动S1PR1受体可影响炎症相关信号通路。本课题拟建立S1PR1受体沉默/高表达人血管内皮细胞株，探究激动S1PR1受体是否通过调控NF-kB、MAPK信号通路影响促炎因子产生；然后使用血管内皮细胞S1PR1基因敲除小鼠，构建流感病毒感染模型，明确血管内皮细胞在流感所致炎症反应中地位。本项目期望通过干预肺内皮细胞S1PR1受体调控炎症反应为临床治疗流感所致ARDS提供新策略。

中文关键词： 肺部感染；炎症反应；流感病毒；肺内皮细胞；S1PR1

英文摘要： nfluenza virus-inducing ARDS following the cytokine storm during influenza infection plays a key role in the motality.Pulmonary endothelium were recently recongnised as an important soure of cytokines.Excitment of S1PR1 on endothelium would efficiently reduced the level of cytokine storm.However, how did excitement of S1PR1 reduce the produce of cytokine in endothelum and which kind of pulmonary endothelium were the key source of cytokine? We have demonstrated that mRNA levels of cykokines were increased after human pulmonary microvascular endotheliar cells were infected by influenza virus.Based on those, we speculate that human vascular endothelium were the main source of cytokine storm and excitement of S1PR1 would influence signal pathways responsible for produce of cytokines.To vertify this hypothesis,we would like to generate the S1PR1 silencing/over-expressing human vascular endothelial cell lines respectively in dissection of the influence of signal pathways responsible for produce of cytokines through the excitment of S1PR1. We will then use vascular endothelial S1PR1 gene knockout mice to illustrate the significance of S1PR1 on vascular endothelium in the regulation of cytokine storm during influenza infection. We anticipate that excitment of S1PR1 on vascular endothelium may become a new strategy for the treatment of influenza virus-inducing ARDS.

英文关键词： lung infection;inflammation;influenza virus;pulmonary endothelium;S1PR1