PMID- 27916734
OWN - NLM
STAT- MEDLINE
DCOM- 20170302
LR  - 20170302
IS  - 1879-0631 (Electronic)
IS  - 0024-3205 (Linking)
VI  - 170
DP  - 2017 Feb 1
TI  - Azithromycin ameliorates airway remodeling via inhibiting airway epithelium 
      apoptosis.
PG  - 1-8
LID - S0024-3205(16)30676-2 [pii]
LID - 10.1016/j.lfs.2016.11.024 [doi]
AB  - AIMS: Azithromycin can benefit treating allergic airway inflammation and 
      remodeling. In the present study, we hypothesized that azithromycin alleviated 
      airway epithelium injury through inhibiting airway epithelium apoptosis via down 
      regulation of caspase-3 and Bax/Bcl2 ratio in vivo and in vitro. MAIN METHODS: 
      Ovalbumin induced rat asthma model and TGF-beta1-induced BEAS-2B cell apoptosis 
      model were established, respectively. In vivo experiments, airway epithelium was 
      stained with hematoxylin and eosin (HE) and periodic acid-Schiff (PAS) to 
      histologically evaluate the airway inflammation and remodeling. Airway epithelium 
      apoptotic index (AI) was further analyzed by terminal deoxynucleotidyl 
      transferase-mediated dUTP nick end labeling (TUNEL), while expression of 
      apoptosis related gene (Bax, Bcl2, Caspase-3) in lungs were measured by qRT-PCR 
      and western blotting, respectively. In vitro experiments, apoptosis were 
      evaluated by Flow cytometry (FCM) and TUNEL. Above apoptosis related gene were 
      also measured by qRT-PCR and western blotting. KEY FINDINGS: Compared with the 
      OVA group, azithromycin significantly reduced the inflammation score, 
      peribronchial smooth muscle layer thickness, epithelial thickening and goblet 
      cell metaplasia (P<0.05), and effectively suppressed AI of airway epithelium 
      (P<0.05). Moreover, the increasing mRNA and protein expressions of Caspase-3 and 
      Bax/Bcl-2 ratio in lung tissue were all significantly decreased in 
      azithromycin-treated rats (P<0.05). In vitro, azithromycin significantly 
      suppressed TGF-beta1-induced BEAS-2B cells apoptosis (P<0.05) and reversed TGF-beta1 
      elevated Caspase-3 mRNA level and Bax/Bcl-2 ratio (P<0.05). SIGNIFICANCE: 
      Azithromycin is an attractive treatment option for reducing airway epithelial 
      cell apoptosis by improving the imbalance of Bax/Bcl-2 ratio and inhibiting 
      Caspase-3 level in airway epithelium.
CI  - Copyright (c) 2016 Elsevier Inc. All rights reserved.
FAU - Liu, Yuanqi
AU  - Liu Y
AD  - Department of Pharmacology, West China School of Preclinical and Forensic 
      Medicine, Sichuan University, Chengdu, Sichuan 610041, PR China; Sichuan 
      University "985 project -- Science and Technology Innovation Platform for Novel 
      Drug Development", Sichuan University, Chengdu, Sichuan 610041, PR China.
FAU - Pu, Yue
AU  - Pu Y
AD  - Department of Pharmacology, West China School of Preclinical and Forensic 
      Medicine, Sichuan University, Chengdu, Sichuan 610041, PR China; Sichuan 
      University "985 project -- Science and Technology Innovation Platform for Novel 
      Drug Development", Sichuan University, Chengdu, Sichuan 610041, PR China.
FAU - Li, Diandian
AU  - Li D
AD  - Department of Respiratory Medicine, West China Hospital, Sichuan University, 
      Chengdu, Sichuan 610041, PR China.
FAU - Zhou, Liming
AU  - Zhou L
AD  - Department of Pharmacology, West China School of Preclinical and Forensic 
      Medicine, Sichuan University, Chengdu, Sichuan 610041, PR China; Sichuan 
      University "985 project -- Science and Technology Innovation Platform for Novel 
      Drug Development", Sichuan University, Chengdu, Sichuan 610041, PR China.
FAU - Wan, Lihong
AU  - Wan L
AD  - Department of Pharmacology, West China School of Preclinical and Forensic 
      Medicine, Sichuan University, Chengdu, Sichuan 610041, PR China; Sichuan 
      University "985 project -- Science and Technology Innovation Platform for Novel 
      Drug Development", Sichuan University, Chengdu, Sichuan 610041, PR China. 
      Electronic address: wanlihong1976@sina.com.
LA  - eng
PT  - Journal Article
DEP - 20161202
PL  - Netherlands
TA  - Life Sci
JT  - Life sciences
JID - 0375521
RN  - 0 (Bax protein, rat)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (Transforming Growth Factor beta1)
RN  - 0 (bcl-2-Associated X Protein)
RN  - 83905-01-5 (Azithromycin)
RN  - 9006-59-1 (Ovalbumin)
RN  - EC 3.4.22.- (Casp3 protein, rat)
RN  - EC 3.4.22.- (Caspase 3)
SB  - IM
MH  - *Airway Remodeling
MH  - Animals
MH  - Apoptosis/*drug effects
MH  - Asthma/*drug therapy/pathology
MH  - Azithromycin/*therapeutic use
MH  - Caspase 3/metabolism
MH  - Cell Line
MH  - Endothelium, Vascular/*drug effects/*pathology
MH  - Epithelium/pathology
MH  - Flow Cytometry
MH  - In Situ Nick-End Labeling
MH  - Inflammation
MH  - Lung/metabolism/pathology
MH  - Male
MH  - Ovalbumin/chemistry
MH  - Proto-Oncogene Proteins c-bcl-2/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Transforming Growth Factor beta1/metabolism
MH  - bcl-2-Associated X Protein/metabolism
OTO - NOTNLM
OT  - Airway epithelium apoptosis
OT  - Azithromycin
OT  - Bax/bcl-2
OT  - Caspase-3
EDAT- 2016/12/06 06:00
MHDA- 2017/03/03 06:00
CRDT- 2016/12/06 06:00
PHST- 2016/10/06 00:00 [received]
PHST- 2016/11/17 00:00 [revised]
PHST- 2016/11/25 00:00 [accepted]
PHST- 2016/12/06 06:00 [pubmed]
PHST- 2017/03/03 06:00 [medline]
PHST- 2016/12/06 06:00 [entrez]
AID - S0024-3205(16)30676-2 [pii]
AID - 10.1016/j.lfs.2016.11.024 [doi]
PST - ppublish
SO  - Life Sci. 2017 Feb 1;170:1-8. doi: 10.1016/j.lfs.2016.11.024. Epub 2016 Dec 2.