title: Antibody to mCLCA3 suppresses symptoms in a mouse model of asthma.
abstract: BACKGROUND
  Asthma is a complex and heterogeneous chronic inflammatory disorder that is associated with mucous cell metaplasia and mucus hypersecretion. Functional genomic analysis indicates that mucous cell metaplasia and mucus hypersecretion depend on members of the calcium-activated chloride channel (CLCA) gene family. It has been reported that the inhibition of CLCAs could relieve the symptoms of asthma. Thus, the mCLCA3 antibody may be a promising strategy to treat allergic diseases such as asthma.
  
  
  METHODS
  We constructed asthmatic mouse models of OVA-induced chronic airway inflammatory disorder to study the function of the mCLCA3 antibody. Airway inflammation was measured by HE staining; goblet cell hyperplasia and mucus hypersecretion were detected by PAS staining; muc5ac, IL-13, IFN-γ levels in bronchoalveolar lavage fluid (BALF) were examined by ELISA; Goblet cell apoptosis was measured by TUNEL assay and alcian blue staining; mCLCA3, Bcl-2 and Bax expression were detected by RT-PCR, Western blotting and immunohistochemical analysis.
  
  
  RESULTS
  In our study, mice treated with mCLCA3 antibody developed fewer pathological changes compared with control mice and asthmatic mice, including a remarkable reduction in airway inflammation, the number of goblet cells and mCLCA3 expression in lung tissue. The levels of muc5ac and IL-13 were significantly reduced in BALF. We also found that the rate of goblet cell apoptosis was increased after treatment with mCLCA3 antibody, which was accompanied by an increase in Bax levels and a decrease in Bcl-2 expression in goblet cells.
  
  
  CONCLUSIONS
  Taken together, our results indicate that mCLCA3 antibody may have the potential as an effective pharmacotherapy for asthma.
authors.affiliation: Department of Pulmonary and Critical Care Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Liqiang
authors.initials: L
authors.lastname: Song
authors.affiliation: Department of Pulmonary and Critical Care Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Dapeng
authors.initials: D
authors.lastname: Liu
authors.affiliation: Department of Pulmonary and Critical Care Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Changgui
authors.initials: C
authors.lastname: Wu
authors.affiliation: Department of Pharmacy, The Fourth Military Medical University, Xi'an, China.
authors.forename: Shouzhen
authors.initials: S
authors.lastname: Wu
authors.affiliation: Department of Pulmonary and Critical Care Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Junlan
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Pulmonary and Critical Care Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Fangping
authors.initials: F
authors.lastname: Ren
authors.affiliation: Department of Cardiovascular Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
mesh_terms: D000818:Animals; D000906:Antibodies / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001249:Asthma / Q000188:drug therapy* / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid; D018118:Chloride Channels / Q000276:immunology*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D020397:Goblet Cells / Q000187:drug effects / Q000473:pathology; D006965:Hyperplasia; D007249:Inflammation / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D055271:Mucin 5AC / Q000378:metabolism; D009088:Mucoproteins / Q000276:immunology*; D010047:Ovalbumin / Q000276:immunology; D012137:Respiratory System / Q000187:drug effects / Q000473:pathology
chemical_list: D000906:Antibodies; D018118:Chloride Channels; C116464:Clca3a1 protein, mouse; D016207:Cytokines; D055271:Mucin 5AC; D009088:Mucoproteins; D010047:Ovalbumin