重组人IL-37通过调控Wnt5a减少细颗粒物诱导的支气管上皮细胞外基质沉积  

Recombinant human IL-37 alleviates PM2.5-induced extracellular matrix deposition in bronchial epithelial cells by regulating Wnt5a

作　　者：曲芳芳[1] 徐海博[1] 齐天杰[1] 蔡志刚[1] 阎锡新[1] QU fangfang;XU haibo;QI Tianjie;CAI Zhigang;YAN Xixin(Department of Respiratory and Critical Care Medicine,The Second Hospital of Hebei Medical University,Shijiazhuang 050000,China)

机构地区：[1]河北医科大学第二医院呼吸与危重症医学一科,河北石家庄050000

出　　处：《中国病理生理杂志》2025年第1期46-53,共8页Chinese Journal of Pathophysiology

基　　金：河北省卫生厅青年科技课题资助项目(No.20190569)。

摘　　要：目的:探讨重组人白细胞介素37(rhIL-37)干预对细颗粒物(PM_(2.5))暴露诱导的人支气管上皮细胞细胞外基质沉积的治疗作用及机制。方法:通过不同浓度(6.25、12.5、25和50 mg/L)的PM_(2.5)干预正常人支气管上皮细胞16HBE建立气道损伤的细胞模型,用Western blot和细胞免疫荧光检测Wnt家族成员5a(Wnt5a)表达水平,选取Wnt5a表达量最高时的PM_(2.5)浓度为最佳干预浓度。实验分为3组:PM_(2.5)+siRNA组、PM_(2.5)+Wnt5a siRNA组及control+Wnt5a siRNA,观察纤连蛋白(fibronectin)、IL-6和IL-1β的表达水平及活性氧(ROS)的产生。此外,又将实验分为PM_(2.5)+rhIL-37组、PM_(2.5)组和control组,研究rhIL-37是否能够下调Wnt5a、fibronectin、IL-6和IL-1β的表达。结果:(1)给予不同浓度(6.25、12.5、25和50 mg/L)的PM_(2.5)干预16HBE细胞24 h后,Wnt5a的表达除PM_(2.5)(50 mg/L)组,均较control组显著增加(P<0.05);在PM_(2.5)(12.5 mg/L)刺激下,Wnt5a表达最高(P<0.01)。(2)在PM_(2.5)(12.5 mg/L)干预16HBE细胞24 h后,fibronectin表达达到峰值(P<0.01)。(3)敲减Wnt5a后fibronectin和核因子E2相关因子2(Nrf2)的表达,ROS的产生,以及IL-6和IL-1β的分泌均较control组显著减少(P<0.01)。(4)rhIL-37干预后再给予PM_(2.5)刺激,Wnt5a、fibronectin和Nrf2的表达,ROS的产生,以及IL-6和IL-1β的分泌均较PM_(2.5)组显著减少(P<0.05)。结论:在体外细胞模型中,PM_(2.5)可能通过Wnt5a调控炎症反应和氧化应激,从而诱导支气管上皮细胞外基质沉积;rhIL-37通过下调Wnt5a减轻炎症反应和氧化应激,从而减少细胞外基质沉积。AIM:To investigate the therapeutic effect of recombinant human interleukin-37(rhIL-37)intervention on extracellular matrix deposition in human bronchial epithelial cells exposed to fine particulate matter(PM_(2.5)),and to explore the underlying mechanisms.METHODS:An airway injury cell model was established using normal human bronchial epithelial 16HBE cells treated with various concentrations(6.25,12.5,25 and 50 mg/L)of PM_(2.5).Western blot and immunofluorescence were employed to assess the expression level of Wnt family member 5a(Wnt5a).The concentration of PM_(2.5) that maximized Wnt5a expression was identified as the optimal concentration for further analysis.The cells were divided into 3 groups,PM_(2.5)+siRNA,PM_(2.5)+Wnt5a siRNA and control+Wnt5a siRNA,to evaluate the expression of fibronectin,the secretion of IL-6 and IL-1β,and the production of reactive oxygen species(ROS).A subsequent set of experiments was organized into PM_(2.5)+rhIL-37,PM_(2.5) and control groups to determine whether rhIL-37 down-regulates the expression of Wnt5a and fibronectin,and reduces the secretion of IL-6 and IL-1β.RESULTS:(1)After 24 h of exposure to various concentrations of PM_(2.5),the expression of Wnt5a in 16HBE cells was significantly elevated,except at 50 mg/L,compared with control group(P<0.05).The highest Wnt5a expression was observed at 12.5 mg/L PM_(2.5)(P<0.01).(2)Fibronectin expression peaked after 24 h of exposure to PM_(2.5) at 12.5 mg/L(P<0.01).(3)Successful knockdown of Wnt5a resulted in decreased levels of fibronectin and nuclear factor E2-related factor(Nrf2).Additionally,the production of ROS and the secretion of IL-6 and IL-1βwere significantly reduced compared with control group(P<0.01).(4)The administration of rhIL-37 before PM_(2.5) exposure led to decreased levels of Wnt5a,fibronectin and Nrf2 compared with PM_(2.5) group(P<0.05).Furthermore,rhIL-37 treatment reduced the ROS production and the secretion of IL-6 and IL-1β(P<0.05).CONCLUSION:In vitro cell models demonstrate that PM_(2.5) can induce e

关 键 词：重组人白细胞介素37 空气污染物 细颗粒物 人支气管上皮细胞 Wnt5a蛋白 

分 类 号：R562.2[医药卫生—呼吸系统] R363[医药卫生—内科学] R122.7[医药卫生—临床医学]