Knockout of IL-17A alleviates airway remodeling in a model of chronic asthma via a p38-dependent pathway
10.3969/j.issn.1000-4718.2025.08.007
- VernacularTitle:敲除哮喘小鼠IL-17A基因通过抑制p38磷酸化减轻气道重塑
- Author:
Xixi LIN
1
;
Yuanyuan ZHANG
;
Qianjin LOU
;
Weixi ZHANG
Author Information
1. 温州医科大学附属第二医院、育英儿童医院药学部,浙江 温州 325027
- Publication Type:Journal Article
- Keywords:
interleukin-17A;
asthma;
airway remodeling;
p38 mitogen-activated protein kinase;
airway smooth muscle cells
- From:
Chinese Journal of Pathophysiology
2025;41(8):1514-1522
- CountryChina
- Language:Chinese
-
Abstract:
AIM:To investigate the ameliorative effect of interleukin 17A(IL-17A)gene knockout on airway remodeling in asthmatic mice and the specific mechanism involved.METHODS:In vivo,wild-type and IL-17A knockout(IL-17A-/-)mice were divided into 4 groups:control,IL-17A-/-,ovalbumin(OVA)and OVA+IL-17A-/-,with 6 mice in each group.Airway hyperresponsiveness was measured,pathological changes in the lungs were observed by staining tissue sections,the expression of the proteins related to airway remodeling,such as α-smooth muscle actin(α-SMA),matrix me-talloproteinase-9(MMP-9)and collagen type Ⅲ(Col Ⅲ),was detected by immunohistochemistry,and the level of p-p38 mitogen-activated protein kinase was detected by Western blot.In vitro,the regulatory effects of IL-17A on transforming growth factor β1(TGF-β1)-induced proliferation and migration of human airway smooth muscle(HASM)cells were as-sessed.Additionally,the level of p38 phosphorylation was detected,and the effect of a p38 inhibitor on airway remodel-ing-related protein expression was evaluated.RESULTS:Knockout of IL-17A significantly attenuated airway hyperrespon-siveness,airway inflammation and downregulated α-SMA(P<0.01),MMP-9(P<0.01)and Col Ⅲ(P<0.01)in asth-matic mice.In HASM cells,the proliferation and migration of these cells were inhibited following IL-17A intervention.Furthermore,a significant reduction in p38 phosphorylation was observed in both mouse lung tissue(P<0.01)and HASM cells(P<0.01).In addition,the gene expression of α-SMA(P<0.05),MMP-9(P<0.01)and Col Ⅲ(P<0.05)was re-duced upon further inhibition of p38 phosphorylation.CONCLUSION:Knockout of IL-17A attenuates airway remodeling in asthmatic mice by inhibiting the phosphorylation of p38 in airway smooth muscle.
