PMID- 31571828
OWN - NLM
STAT- MEDLINE
DCOM- 20200225
LR  - 20220410
IS  - 1177-8881 (Electronic)
IS  - 1177-8881 (Linking)
VI  - 13
DP  - 2019
TI  - Carbocisteine inhibits the expression of Muc5b in COPD mouse model.
PG  - 3259-3268
LID - 10.2147/DDDT.S198874 [doi]
AB  - 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.
CI  - (c) 2019 Song et al.
FAU - Song, Yan
AU  - Song Y
AD  - State 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.
FAU - Wang, Wei
AU  - Wang W
AD  - Drug Research Institute of Guangzhou BaiYunShan Pharmaceutical General Factory, 
      Guangzhou, 510515, People's Republic of China.
FAU - Xie, Yanqing
AU  - Xie Y
AD  - State 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.
FAU - Xiang, Bin
AU  - Xiang B
AD  - State 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.
FAU - Huang, Xuan
AU  - Huang X
AD  - State 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.
FAU - Guan, Weijie
AU  - Guan W
AD  - State 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.
FAU - Zheng, Jinping
AU  - Zheng J
AD  - State 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.
LA  - eng
PT  - Journal Article
DEP - 20190916
PL  - New Zealand
TA  - Drug Des Devel Ther
JT  - Drug design, development and therapy
JID - 101475745
RN  - 0 (Chemokines)
RN  - 0 (Interleukin-6)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Muc5b protein, mouse)
RN  - 0 (Mucin 5AC)
RN  - 0 (Mucin-5B)
RN  - 147037-79-4 (keratinocyte-derived chemokines)
RN  - 740J2QX53R (Carbocysteine)
SB  - IM
MH  - Animals
MH  - Carbocysteine/*therapeutic use
MH  - Chemokines/metabolism
MH  - Cigarette Smoking/adverse effects
MH  - Disease Models, Animal
MH  - Emphysema/prevention & control
MH  - Inflammation/drug therapy/metabolism
MH  - Interleukin-6/metabolism
MH  - Lipopolysaccharides/administration & dosage
MH  - Lung/immunology/metabolism/pathology
MH  - Mice
MH  - Mucin 5AC/*metabolism
MH  - Mucin-5B/*metabolism
MH  - Mucus/metabolism
MH  - Pulmonary Disease, Chronic Obstructive/*drug therapy/immunology
PMC - PMC6754527
OTO - NOTNLM
OT  - COPD
OT  - Muc5ac
OT  - Muc5b
OT  - carbocisteine
OT  - cigarette smoke
COIS- The abstract has been submitted to the 22nd Congress of the Asian Pacific Society 
      of Respirology, International Convention Centre, Sydney, Australia, 23-26 
      November 2017 and has been published in Respirology, Vol 22 Issue S3. The authors 
      report no other conflicts of interest in this work.
EDAT- 2019/10/02 06:00
MHDA- 2020/02/26 06:00
PMCR- 2019/09/16
CRDT- 2019/10/02 06:00
PHST- 2019/01/03 00:00 [received]
PHST- 2019/07/12 00:00 [accepted]
PHST- 2019/10/02 06:00 [entrez]
PHST- 2019/10/02 06:00 [pubmed]
PHST- 2020/02/26 06:00 [medline]
PHST- 2019/09/16 00:00 [pmc-release]
AID - 198874 [pii]
AID - 10.2147/DDDT.S198874 [doi]
PST - epublish
SO  - Drug Des Devel Ther. 2019 Sep 16;13:3259-3268. doi: 10.2147/DDDT.S198874. 
      eCollection 2019.