Open Access

ARTICLE

IL-27 attenuates airway inflammation and epithelialmesenchymal transition in allergic asthmatic mice possibly via the RhoA/ROCK signalling pathway

Chuanjun Huang^1,2, Yan Sun², Na Liu², Ziping Zhang¹, Xiyan Wang², Degan Lu², Ling Zhou^2,a, Caiqing Zhang^3,a

1 Department of Respiratory Diseases, Shandong University of Traditional Chinese Medicine, Jinan, Shandong 250013
2 Department of Respiratory Medicine and critical care, The First Affiliated Hospital of Shandong First Medical University & Shandong Provincial Qianfoshan Hospital, Jinan, Shandong 250014
3 Department of Respiratory Diseases, Department of Otolaryngology-Head and Neck Surgery, Shandong Provincial ENT Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250014
a The authors contributed equally

* Corresponding Authors: Caiqing Zhang, Ling Zhou, ,

European Cytokine Network 2022, 33(1), 13-24. https://doi.org/10.1684/ecn.2021.0476

Accepted 14 May 2022;

Abstract

Background: Asthma is an airway disease characterized by airflow limitation and various additional clinical manifestations. Repeated inflammatory stimulation of the airways leads to epithelial-mesenchymal transition (EMT) which aggravates subepithelial fibrosis during the process of airway remodelling and enhances resistance to corticosteroids and bronchodilators in refractory asthma. There is growing evidence that IL-27 modulates airway remodelling, however, the molecular mechanisms involving IL-27 and EMT are poorly understood. The objective of this study was to investigate the effects of IL-27 on ovalbumin (OVA)-challenged asthmatic mice in vivo and TGF-β1-induced EMT in 16HBE cells in vitro. METHODS: Airway inflammation, mucus secretion, and collagen deposition were analysed by conventional pathological techniques. The ratio of Th17 and Th9 cells in the spleen of mice was measured using flow cytometry, ELISA was performed for cytokine analysis to identify EMT-related molecules and signalling pathways, and other molecular and cellular techniques were used to explore the functional mechanism involving IL-27 and EMT. RESULTS: Airway inflammation in asthmatic mice was significantly alleviated by IL-27, with downregulation of RhoA and ROCK, upregulation of E-cadherin, and a decrease of vimentin and α-SMA expression, compared to asthmatic mice. Moreover, the frequency of Th17 and Th9 cells in the spleen of asthmatic mice decreased following treatment with IL-27. In TGF-β1-induced 16HBE cells, the addition of IL-27 was shown to inhibit EMT, based on the expression of E-cadherin, vimentin, and α-SMA. CONCLUSION: Intranasal administration of IL-27 attenuates airway inflammation and EMT in a murine model of allergic asthma possibly by downregulating the RhoA/ROCK signalling pathway.

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