title: Inhalation of glycopyrronium inhibits cigarette smoke-induced acute lung inflammation in a murine model of COPD.
abstract: Glycopyrronium bromide (GB) is a muscarinic receptor antagonist that has been used as a long-acting bronchodilator in chronic obstructive pulmonary disease (COPD) patients. The aim of this study was to investigate the anti-inflammatory activity of inhaled GB in a cigarette smoke-induced acute lung inflammation mouse model. We found that aerosol pre-treatment with GB suppresses the accumulation of neutrophils and macrophages in the bronchoalveolar lavage fluid (BALF) in cigarette smoke (CS)-exposed mice. GB at doses of 300 and 600 μg/ml significantly inhibited the CS-induced increases in the mRNA and protein expression levels of interleukin (IL)-1β, tumor necrosis factor (TNF)-α, monocyte chemotactic protein (MCP)-1 and transforming growth factor (TGF)-β1 in lung tissues and the BALF. Moreover, GB at a dose of 600 μg/ml significantly inhibited the CS-induced changes in glutathione (GSH) and myeloperoxidase (MPO) activities in the BALF, decreased the CS-induced expression of matrix metalloproteinases (MMP)-9, and increased the CS-induced expression of tissue inhibitor of metalloproteinases (TIMP)-1, as determined through the immunohistochemical staining of lung tissue. Our results demonstrate the beneficial effects of inhaled GB on the inflammatory reaction in COPD.
authors.affiliation: Medical College, Yangzhou University, 11 Huaihai Road, Yangzhou City, Jiangsu Province, 225001, China; Zhejiang Respiratory Drugs Research Laboratory of State Food and Drug Administration of China, Medicine School of Zhejiang University, Hangzhou 310058, China.
authors.forename: Liang-liang
authors.initials: LL
authors.lastname: Shen
authors.affiliation: Medical College, Yangzhou University, 11 Huaihai Road, Yangzhou City, Jiangsu Province, 225001, China; Zhejiang Respiratory Drugs Research Laboratory of State Food and Drug Administration of China, Medicine School of Zhejiang University, Hangzhou 310058, China.
authors.forename: Ya-nan
authors.initials: YN
authors.lastname: Liu
authors.affiliation: Zhejiang Respiratory Drugs Research Laboratory of State Food and Drug Administration of China, Medicine School of Zhejiang University, Hangzhou 310058, China.
authors.forename: Hui-juan
authors.initials: HJ
authors.lastname: Shen
authors.affiliation: Shanghai Institute of Pharmaceutical Industry, Shanghai 200040, China.
authors.forename: Chong
authors.initials: C
authors.lastname: Wen
authors.affiliation: Zhejiang Respiratory Drugs Research Laboratory of State Food and Drug Administration of China, Medicine School of Zhejiang University, Hangzhou 310058, China.
authors.forename: Yong-liang
authors.initials: YL
authors.lastname: Jia
authors.affiliation: Zhejiang Respiratory Drugs Research Laboratory of State Food and Drug Administration of China, Medicine School of Zhejiang University, Hangzhou 310058, China.
authors.forename: Xin-wei
authors.initials: XW
authors.lastname: Dong
authors.affiliation: Shanghai Institute of Pharmaceutical Industry, Shanghai 200040, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Jin
authors.affiliation: Jiashilianbo Medicine Science & Technique Co., Beijing 100080, China.
authors.forename: Xiao-ping
authors.initials: XP
authors.lastname: Chen
authors.affiliation: Medical College, Yangzhou University, 11 Huaihai Road, Yangzhou City, Jiangsu Province, 225001, China. Electronic address: jgz7718@sina.com.
authors.forename: Yun
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Zhejiang Respiratory Drugs Research Laboratory of State Food and Drug Administration of China, Medicine School of Zhejiang University, Hangzhou 310058, China; Laboratory Animal Center of Zhejiang University, Hangzhou 310058, China. Electronic address: xieqm@zju.edu.cn.
authors.forename: Qiang-min
authors.initials: QM
authors.lastname: Xie
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D016207:Cytokines / Q000235:genetics / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D006024:Glycopyrrolate / Q000494:pharmacology / Q000627:therapeutic use*; D008214:Lymphocytes / Q000276:immunology; D008264:Macrophages / Q000276:immunology; D020780:Matrix Metalloproteinase 9 / Q000276:immunology; D051379:Mice; D008813:Mice, Inbred ICR; D018727:Muscarinic Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D009504:Neutrophils / Q000276:immunology; D018384:Oxidative Stress / Q000187:drug effects; D011014:Pneumonia / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000276:immunology; D012906:Smoke; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000276:immunology; D014026:Nicotiana
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D018727:Muscarinic Antagonists; D012906:Smoke; C560825:Timp1 protein, mouse; D019715:Tissue Inhibitor of Metalloproteinase-1; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse; D006024:Glycopyrrolate
keywords: Airway inflammation; COPD; Cigarette smoke; Drug delivery; Glycopyrronium bromide; Muscarinic receptor antagonist