title: Therapeutic effects of histone deacetylase inhibitors in a murine asthma model.
abstract: OBJECTIVE
  To investigate the therapeutic effects of various HDAC inhibitors on the development of chronic allergic airway disease in mice with airway inflammation, airway remodeling, and airway hyperresponsiveness.
  
  
  METHODS
  Wild-type BALB/C mice (N = 72).
  
  
  METHODS
  Tubastatin A HCl [TSA, a selective histone deacetylase 6 (HDAC6) inhibitor], PCI-34051 (a selective HDAC8 inhibitor), and givinostat (a broad-spectrum HDAC inhibitor that inhibits class I and class II HDACs and several pro-inflammatory cytokines).
  
  
  METHODS
  Mice were divided into six groups: control, asthma, dexamethasone (positive control), TSA, PCI-34051, and givinostat (n = 12 per group). Twenty-four hours after OVA nebulization, airway hyperresponsiveness, inflammation, and remodeling were assessed.
  
  
  RESULTS
  The chronic asthma mouse model produced typical airway inflammation, airway remodeling, and airway hyperresponsiveness. Administration of PCI-34051 and dexamethasone reduced the eosinophilic inflammation and airway hyperresponsiveness in asthma to reduce the airway remodeling. Treatment with Tubastatin A HCl reduced airway inflammation and was associated with decreased IL-4, IL-5 and total inflammatory cell count, as well as goblet cell metaplasia and subepithelial fibrosis; however, this outcome was not as effective as that with dexamethasone. TGF-β1 expression in the cytoplasm of airway epithelium of mice in the Tubastatin A HCl group was reduced and expression of α-SMA in the airway smooth muscle was also decreased.
  
  
  CONCLUSIONS
  The results suggested that treatment with HDAC inhibitors can reduce airway inflammation, airway remodeling, and airway hyperresponsiveness in chronic allergic airway disease in mice.
authors: Department of Respiratory Medicine, Institute of Respiratory Diseases, The First Affiliated Hospital of China Medical University, 155 North Nanjing Street, Shenyang, 110001, People's Republic of China.
authors: Yuan
authors: Y
authors: Ren
authors: Department of Respiratory Medicine, Institute of Respiratory Diseases, The First Affiliated Hospital of China Medical University, 155 North Nanjing Street, Shenyang, 110001, People's Republic of China. xinming_med@126.com.
authors: Xinming
authors: X
authors: Su
authors: Department of Respiratory Medicine, Institute of Respiratory Diseases, The First Affiliated Hospital of China Medical University, 155 North Nanjing Street, Shenyang, 110001, People's Republic of China.
authors: Lingfei
authors: L
authors: Kong
authors: Department of Respiratory Medicine, Institute of Respiratory Diseases, The First Affiliated Hospital of China Medical University, 155 North Nanjing Street, Shenyang, 110001, People's Republic of China.
authors: Menglu
authors: M
authors: Li
authors: Department of Respiratory Medicine, Institute of Respiratory Diseases, The First Affiliated Hospital of China Medical University, 155 North Nanjing Street, Shenyang, 110001, People's Republic of China.
authors: Xuan
authors: X
authors: Zhao
authors: Department of Respiratory Medicine, Institute of Respiratory Diseases, The First Affiliated Hospital of China Medical University, 155 North Nanjing Street, Shenyang, 110001, People's Republic of China.
authors: Na
authors: N
authors: Yu
authors: Department of Respiratory Medicine, Institute of Respiratory Diseases, The First Affiliated Hospital of China Medical University, 155 North Nanjing Street, Shenyang, 110001, People's Republic of China. kangjian58@163.com.
authors: Jian
authors: J
authors: Kang
mesh_terms: D000199:Actins / Q000378:metabolism; D056151:Airway Remodeling / Q000187:drug effects; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D003094:Collagen / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D006877:Hydroxamic Acids / Q000494:pharmacology / Q000627:therapeutic use; D007211:Indoles / Q000494:pharmacology / Q000627:therapeutic use; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D000199:Actins; D018927:Anti-Asthmatic Agents; D016207:Cytokines; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D007211:Indoles; C529435:PCI 34051; D053773:Transforming Growth Factor beta1; C553587:tubastatin A; D003094:Collagen
keywords: Airway hyperresponsiveness; Airway inflammation; Bronchial asthma; Histone deacetylase