Decreased epithelial and sputum miR-221-3p associates with airway eosinophilic inflammation and CXCL17 expression in asthma

• Published in: American journal of physiology. Lung cellular and molecular physiology Vol. 315; no. 2; pp. L253 - L264
• Main Authors: Zhang, Kan, Liang, Yuxia, Feng, Yuchen, Wu, Wenliang, Zhang, Huilan, He, Jianguo, Hu, Qinghua, Zhao, Jianping, Xu, Yongjian, Liu, Zheng, Zhen, Guohua
• Format: Journal Article
• Language: English
• Published: United States 01.08.2018
• Subjects: Adult; Asthma - blood; Asthma - pathology; Biomarkers - blood; Cell Adhesion Molecules - blood; Cell Line; Chemokine CCL24 - blood; Chemokine CCL26 - blood; Chemokines - blood; Eosinophils - metabolism; Eosinophils - pathology; Female; Humans; Inflammation - blood; Inflammation - pathology; Male; MAP Kinase Signaling System; MicroRNAs - blood; Mouth Mucosa - metabolism; Mouth Mucosa - pathology; Real-Time Polymerase Chain Reaction; Sputum - metabolism; Up-Regulation; CXCL17; eosinophilia; epithelial cells; microRNA; asthma
• ISSN: 1040-0605; 1522-1504; 1522-1504
• DOI: 10.1152/ajplung.00567.2017

Airway eosinophilic inflammation is a key feature of type 2 high asthma. The role of epithelial microRNA (miR) in airway eosinophilic inflammation remains unclear. We examined the expression of miR-221-3p in bronchial brushings, induced sputum, and plasma from 77 symptomatic, recently diagnosed, steroid-naive subjects with asthma and 36 healthy controls by quantitative PCR and analyzed the correlation between miR-221-3p expression and airway eosinophilia. We found that epithelial, sputum, and plasma miR-221-3p expression was significantly decreased in subjects with asthma. Epithelial miR-221-3p correlated with eosinophil in induced sputum and bronchial biopsies, fraction of exhaled nitric oxide, blood eosinophil, epithelial gene signature of type 2 status, and methacholine provocative dosage required to cause a 20% decline in forced expiratory volume in the first second in subjects with asthma. Sputum miR-221-3p also correlated with airway eosinophilia and was partially restored after inhaled corticosteroid treatment. Inhibition of miR-221-3p expression suppressed chemokine (C-C motif) ligand (CCL) 24 (eotaxin-2), CCL26 (eotaxin-3), and periostin (POSTN) expression in BEAS-2B bronchial epithelial cells. We verified that chemokine (C-X-C motif) ligand (CXCL) 17, an anti-inflammatory chemokine, is a target of miR-221-3p, and epithelial CXCL17 expression significantly increased in asthma. CXCL17 inhibited CCL24, CCL26, and POSTN expression via the p38 MAPK pathway. Airway overexpression of miR-221-3p exacerbated airway eosinophilic inflammation, suppressed CXCL17 expression, and enhanced CCL24, CCL26, and POSTN expression in house dust mite-challenged mice. Taken together, epithelial and sputum miR-221-3p are novel biomarkers for airway eosinophilic inflammation in asthma. Decreased epithelial miR-221-3p may protect against airway eosinophilic inflammation by upregulating anti-inflammatory chemokine CXCL17.