Carbocisteine inhibits the expression of Muc5b in COPD mouse model
Authors Song Y, Wang W, Xie Y, Xiang B, Huang X, Guan W, Zheng J
Received 3 January 2019
Accepted for publication 12 July 2019
Published 16 September 2019 Volume 2019:13 Pages 3259—3268
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Melinda Thomas
Peer reviewer comments 2
Editor who approved publication: Professor Manfred Ogris
Yan Song,1 Wei Wang,2 Yanqing Xie,1 Bin Xiang,1 Xuan Huang,1 Weijie Guan,1 Jinping Zheng1
1State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, People’s Republic of China; 2Drug Research Institute of Guangzhou BaiYunShan Pharmaceutical General Factory, Guangzhou, 510515, People’s Republic of China
Correspondence: Jinping Zheng
First Affiliated Hospital of Guangzhou Medical University, No 151 Yanjiang Road, Guangzhou 510120, People’s Republic of China
Tel +86 208 306 2869
Fax +86 208 306 2729
Background: Cigarette smoke (CS) results in chronic mucus hypersecretion and airway inflammation, contributing to COPD pathogenesis. Mucin 5B (MUC5B) and mucin 5 AC (MUC5AC) are major mucins implicated in COPD pathogenesis. Carbocisteine can reduce mucus viscosity and elasticity. Although carbocisteine decreased human elastase-induced MUC5AC expression in vitro and reduced MUC5AC expression that alleviated bacteria adhesion and improved mucus clearance in vivo, the roles of carbocisteine in inducing MUC5B expression in COPD remain unclear.
Methods: To investigate the Muc5b/Muc5ac ratio and the gene and protein levels of Muc5b in COPD and carbocisteine intervention models. C57B6J mice were used to develop COPD model by instilling intratracheally with lipopolysaccharide on days 1 and 14 and were exposed to CS for 2 hr twice a day for 12 weeks. Low and high doses of carbocisteine 112.5 and 225 mg/kg/d, respectively, given by gavage administration were applied for the treatment in COPD models for the same duration, and carboxymethylcellulose was used as control. Carbocisteine significantly attenuated inflammation in bronchoalveolar lavage fluid and pulmonary tissue, improved pulmonary function and protected against emphysema.
Results: High-dose carbocisteine significantly decreased the overproduction of Muc5b (P<0.01) and Muc5ac (P<0.001), and restored Muc5b/Muc5ac ratio in COPD model group (P<0.001). Moreover, the Muc5b/Muc5ac ratio negatively correlated with pro-inflammatory cytokines such as IL-6 and keratinocyte-derived cytokine, mean linear intercept, functional residual capacity and airway resistance, but positively correlated with dynamic compliance.
Conclusions: These findings suggest that carbocisteine attenuated Muc5b and Muc5ac secretion and restored Muc5b protein levels, which may improve mucus clearance in COPD.
Keywords: COPD, cigarette smoke, Muc5b, Muc5ac, carbocisteine
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