Inhalation of glycopyrronium inhibits cigarette smoke-induced acute lung inflammation in a murine model of COPD |
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| Affiliation: | 1. Medical College, Yangzhou University, 11 Huaihai Road, Yangzhou City, Jiangsu Province, 225001, China;2. Zhejiang Respiratory Drugs Research Laboratory of State Food and Drug Administration of China, Medicine School of Zhejiang University, Hangzhou 310058, China;3. Shanghai Institute of Pharmaceutical Industry, Shanghai 200040, China;4. Jiashilianbo Medicine Science & Technique Co., Beijing 100080, China;5. Laboratory Animal Center of Zhejiang University, Hangzhou 310058, China;1. The Second Affiliated Hospital, Medical College of Zhejiang University, Hangzhou 310009, China;2. Zhejiang Respiratory Drugs Research Laboratory of State Food and Drug Administration of China, Medical College of Zhejiang University, Hangzhou 310058, China;3. Pharmacy College of Zhejiang Chinese Medical University, Hangzhou 310053, China;4. Laboratory Animal Center of Zhejiang University, Hangzhou 310058, China;1. Istituto di Biomedicina e Immunologia Molecolare, Consiglio Nazionale delle Ricerche, Palermo, Italy;2. Fondazione Ri.MED, Palermo, Italy;1. The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China;2. Zhejiang Respiratory Drugs Research Laboratory of State Food and Drug Administration of China, Zhejiang University School of Medicine, Hangzhou 310058, China |
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| 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. |
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