title: Azithromycin ameliorates airway remodeling via inhibiting airway epithelium apoptosis.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  Ovalbumin induced rat asthma model and TGF-β1-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.
  
  
  RESULTS
  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-β1-induced BEAS-2B cells apoptosis (P<0.05) and reversed TGF-β1 elevated Caspase-3 mRNA level and Bax/Bcl-2 ratio (P<0.05).
  
  
  CONCLUSIONS
  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.
authors.affiliation: 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.
authors.forename: Yuanqi
authors.initials: Y
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Yue
authors.initials: Y
authors.lastname: Pu
authors.affiliation: Department of Respiratory Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, PR China.
authors.forename: Diandian
authors.initials: D
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Liming
authors.initials: L
authors.lastname: Zhou
authors.affiliation: 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.
authors.forename: Lihong
authors.initials: L
authors.lastname: Wan
mesh_terms: D056151:Airway Remodeling; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001249:Asthma / Q000188:drug therapy* / Q000473:pathology; D017963:Azithromycin / Q000627:therapeutic use*; D053148:Caspase 3 / Q000378:metabolism; D002460:Cell Line; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000473:pathology*; D004848:Epithelium / Q000473:pathology; D005434:Flow Cytometry; D020287:In Situ Nick-End Labeling; D007249:Inflammation; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008297:Male; D010047:Ovalbumin / Q000737:chemistry; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C494828:Bax protein, rat; D019253:Proto-Oncogene Proteins c-bcl-2; D053773:Transforming Growth Factor beta1; D051028:bcl-2-Associated X Protein; D017963:Azithromycin; D010047:Ovalbumin; C505410:Casp3 protein, rat; D053148:Caspase 3
keywords: Airway epithelium apoptosis; Azithromycin; Bax/bcl-2; Caspase-3