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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
【摘要】 目的:探讨重组人白细胞介素37(rhIL-37)干预对细颗粒物(PM2.5)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PM2.5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PM2.5浓度为最佳干预浓度。实验分为3组:PM2.5+siRNA组、PM2.5+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PM2.5+rhIL-37组、PM2.5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PM2.5干预16HBE细胞24 h后,Wnt5a的表达除PM2.5(50 mg/L)组,均较control组显著增加(P<0.05);在PM2.5(12.5 mg/L)刺激下,Wnt5a表达最高(P<0.01)。(2)在PM2.5(12.5mg/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PM2.5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PM2.5组显著减少(P<0.05)。结论:在体外细胞模型中,PM2.5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。
【Abstract】 AIM:To investigate the therapeutic effect of recombinant human interleukin-37 (rhIL-37) inter?vention on extracellular matrix deposition in human bronchial epithelial cells exposed to fine particulate matter (PM2.5),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 PM2.5.Western blot and immunofluorescence were employed to assess the expression level of Wnt family member 5a (Wnt5a).The con?centration of PM2.5 that maximized Wnt5a expression was identified as the optimal concentration for further analysis.Thecells were divided into 3 groups,PM2.5+siRNA,PM2.5+Wnt5a siRNA and control+Wnt5a siRNA,to evaluate the expres?sion 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 PM2.5+rhIL-37,PM2.5 and control groups to determine whether rhIL-37 down-regu?lates 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 PM2.5,the expression of Wnt5a in 16HBE cells was significantly elevated,except at50 mg/L,compared with control group (P<0.05).The highest Wnt5a expression was observed at 12.5 mg/L PM2.5 (P<0.01).(2) Fibronectin expression peaked after 24 h of exposure to PM2.5 at 12.5 mg/L (P<0.01).(3) Successful knock?down 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-1β were significantly reduced compared with control group (P<0.01).(4) The administration of rhIL-37 before PM2.5 exposure led to decreased levels of Wnt5a,fibronectin and Nrf2 compared with PM2.5 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 PM2.5 can induce extracellular matrix deposition in bronchial epithelial cells,potentially through the modulation of inflammatory response and oxidative stress influenced by Wnt5a.Additionally,rhIL-37 appears to mitigate inflammatory response and oxidative stress by down-regulating Wnt5a.
【Key words】 recombinant human interleukin-37; air pollutant; fine particulate matter; human bronchial epithelial cells; Wnt5a protein;
- 【文献出处】 中国病理生理杂志 ,Chinese Journal of Pathophysiology , 编辑部邮箱 ,2025年01期
- 【分类号】R363
- 【下载频次】24