title: SP600125 promotes resolution of allergic airway inflammation via TLR9 in an OVA-induced murine acute asthma model.
abstract: BACKGROUND
  c-Jun N-terminal kinase (JNK) relays extracellular stimuli through phosphorylation cascades that lead to various cell responses. In the present study, we aimed to investigate the effect of the JNK inhibitor SP600125 on the resolution of airway inflammation, and the underlying mechanism using a murine acute asthma model.
  
  
  METHODS
  Female C57BL/6 mice were sensitized with saline or ovalbumin (OVA) on day 0, and challenged with OVA on day 14-20. Meanwhile, some of the mice were treated with SP600125 (30 mg/kg) intraperitoneally 2 h before each challenge. The airway inflammation was evaluated by counting the numbers of various types of inflammatory cells in bronchoalveolar lavage fluid (BALF), histopathology, cytokines production and mucus secretion in individual mouse. In addition, we analyzed the protein levels of phosphorylated JNK and TLR9 in the lung tissues.
  
  
  RESULTS
  SP600125 markedly reduced the invasion of inflammatory cells into the peribronchial regions, and decreased the numbers of eosinophils, monocytes, neutrophils and lymphocytes in BALF. SP600125 also reduced the level of plasma OVA-specific IgE, lowered the production of pro-inflammatory cytokines in BALF and alleviated mucus secretion. Meanwhile, SP600125 inhibited OVA-induced, increased expression of p-JNK and TLR9 in the lung tissues.
  
  
  CONCLUSIONS
  Collectively, our data demonstrated that SP600125 promoted resolution of allergic airway inflammation via TLR9 in an OVA-induced murine acute asthma model. The JNK-TLR9 pathway may be a new therapeutic target in the treatment for the allergic asthma.
authors.affiliation: Anhui Geriatric Institute, Department of Pulmonary, The First Affiliated Hospital of Anhui Medical University, Jixi Road 218, Hefei, Anhui 230022, PR China.
authors.forename: Hui-Mei
authors.initials: HM
authors.lastname: Wu
authors.affiliation: Anhui Geriatric Institute, Department of Pulmonary, The First Affiliated Hospital of Anhui Medical University, Jixi Road 218, Hefei, Anhui 230022, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Fang
authors.affiliation: Anhui Geriatric Institute, Department of Pulmonary, The First Affiliated Hospital of Anhui Medical University, Jixi Road 218, Hefei, Anhui 230022, PR China.
authors.forename: Qi-Ying
authors.initials: QY
authors.lastname: Shen
authors.affiliation: Anhui Geriatric Institute, Department of Pulmonary, The First Affiliated Hospital of Anhui Medical University, Jixi Road 218, Hefei, Anhui 230022, PR China. Electronic address: rongyuliu@163.com.
authors.forename: Rong-Yu
authors.initials: RY
authors.lastname: Liu
mesh_terms: D000208:Acute Disease; D000818:Animals; D000873:Anthracenes / Q000494:pharmacology / Q000627:therapeutic use*; D001249:Asthma / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D002452:Cell Count; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D005260:Female; D006967:Hypersensitivity / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D007073:Immunoglobulin E / Q000097:blood; D007249:Inflammation / Q000097:blood / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008168:Lung / Q000187:drug effects / Q000201:enzymology / Q000473:pathology*; D008810:Mice, Inbred C57BL; D009093:Mucus / Q000378:metabolism; D010047:Ovalbumin; D010766:Phosphorylation / Q000187:drug effects; D051217:Toll-Like Receptor 9 / Q000378:metabolism*
chemical_list: D000873:Anthracenes; D016207:Cytokines; D051217:Toll-Like Receptor 9; C432165:pyrazolanthrone; D007073:Immunoglobulin E; D010047:Ovalbumin; D048031:JNK Mitogen-Activated Protein Kinases
keywords: Acute asthma; Allergic airway inflammation; JNK; SP600125; TLR9