Recombinant human IL-37 alleviates PM2.5-induced extracellular matrix deposition in bronchial epithelial cells by regulating Wnt5a
10.3969/j.issn.1000-4718.2025.01.006
- VernacularTitle: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
- Author:
Fangfang QU
1
;
Haibo XU
1
;
Tianjie QI
1
;
Zhigang CAI
1
;
Xixin YAN
1
Author Information
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
- Publication Type:Journal Article
- Keywords:
recombinant human interleukin-37;
air pollutant;
fine particulate matter;
human bronchial epi-thelial cells;
Wnt5a protein
- From:
Chinese Journal of Pathophysiology
2025;41(1):46-53
- CountryChina
- Language:Chinese
-
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.The cells 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 at 50 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.
