Mechanism of airway epithelial barrier injury in a mouse model of COPD induced by cigarette smoke exposure combined with Poly I:C
10.3969/j.issn.1000-4718.2024.07.009
- VernacularTitle:香烟烟雾联合Poly I:C诱导COPD模型小鼠气道上皮屏障损伤的机制
- Author:
Yuan XIE
1
;
Xiaofeng MEI
;
Liuying TAO
;
Yuhang JIANG
;
Jiansheng LI
;
Peng ZHAO
Author Information
1. 河南中医药大学呼吸疾病中医药防治省部共建协同创新中心,河南省中医药防治呼吸病重点实验室,河南 郑州 450046
- Keywords:
Chronic obstructive pulmonary disease;
cigarette smoke;
polyinosinic-polycytidylic acid;
airway epithelial barrier
- From:
Chinese Journal of Pathophysiology
2024;40(7):1222-1229
- CountryChina
- Language:Chinese
-
Abstract:
AIM:To establish a mouse model of chronic obstructive pulmonary disease(COPD)induced by cigarette smoke(CS)exposure combined with polyinosinic-polycytidylic acid(Poly I:C)nasal drip,and to investigate the mechanism of airway epithelial barrier injury in COPD.METHODS:(1)Ninety-six male BALB/c mice were randomly divided into control group,CS group,Poly I:C group,and CS+Poly I:C group(n=24).The model was established from week 1 to week 8,with pulmonary function tested every 4 weeks.Six mice from each group were sacrificed at the end of weeks 4,8,16,and 24.Changes in minute volume(MV),enhanced pause(Penh),mean linear intercept(MLI)and bronchial wall thickness(BWT)were observed.The protein levels of interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α),zonula occludens-1(ZO-1)and E-cadherin(E-Cad)in the lung were detected.(2)Human bronchial epithe-lial BEAS-2B cells were stimulated with CS extract(CSE)combined with Poly I:C for 24 h,and then the protein levels of occludin(Occ),ZO-1,and phosphorylated epidermal growth factor receptor(EGFR),P38 and extracellular signal-regu-lated kinase(ERK)1/2 were analyzed.RESULTS:(1)Compared with control group,at the 8th week,the mice in CS and CS+Poly I:C groups showed typical pathological changes in lung tissues,including significant inflammatory cell infil-tration,alveolar cavity expansion,alveolar wall rupture and fusion,and airway wall thickening.The Penh,BWT,MLI,and lung IL-1β and TNF-α levels were significantly increased(P<0.05 or P<0.01),while MV and lung ZO-1 and E-Cad levels were remarkably decreased(P<0.05 or P<0.01).By the 24th week,these pathological changes remained relative-ly stable in CS+Poly I:C group.(2)Compared with control group,CSE and its combination with Poly I:C dramatically in-duced a reduction in ZO-1 and Occ protein expression in BEAS-2B cells(P<0.05 or P<0.01),and increased the levels of phosphorylated EGFR,P38 and ERK1/2(P<0.01).The effects in CSE combined with Poly I:C group were considerably superior to those in CSE or Poly I:C group alone.CONCLUSION:Poly I:C can enhance the pathological changes and airway epithelial barrier damage induced by CS in a mouse model of COPD,which may be related to the activation of EGFR/ERK/P38 signaling pathway.
