title: Murine calcium-activated chloride channel family member 3 induces asthmatic airway inflammation independently of allergen exposure.
abstract: BACKGROUND
  Expression of murine calcium-activated chloride channel family member 3 (mCLCA3) has been reported to be increased in the airway epithelium of asthmatic mice challenged with ovalbumin (OVA). However, its role in asthmatic airway inflammation under no OVA exposure has not yet been clarified.
  
  
  METHODS
  mCLCA3 plasmids were transfected into the airways of normal BALB/c mice. mCLCA3 expression and airway inflammation in mouse lung tissue were evaluated. Cell differentials and cytokines in bronchoalveolar lavage fluid (BALF) were analyzed. The expression of mCLCA3 protein and mucus protein mucin-5 subtype AC (MUC5AC) were analyzed by Western blotting. The mRNA levels of mCLCA3, MUC5AC and interleukin-13 (IL-13) were determined quantitatively.
  
  
  RESULTS
  mCLCA3 expression was not detected in the control group while strong immunoreactivity was detected in the OVA and mCLCA3 plasmid groups, and was strictly localized to the airway epithelium. The numbers of inflammatory cells in lung tissue and BALF were increased in both mCLCA3 plasmid and OVA groups. The protein and mRNA levels of mCLCA3 and MUC5AC in the lung tissue were significantly increased in the mCLCA3 plasmid and OVA groups compared to the control group. The level of IL-13, but not IL-4, IL-5, IFN-γ, CCL2, CCL5 or CCL11, was significantly increased compared with control group in BALF in the mCLCA3 plasmid and OVA groups. The level of IL-13 in the BALF in the mCLCA3 plasmid group was much higher than that in the OVA group (P < 0.05). The level of mCLCA3 mRNA in lung tissue was positively correlated with the levels of MUC5AC mRNA in lung tissue, IL-13 mRNA in lung tissue, the number of eosinophils in BALF, and the content of IL-13 protein in BALF. The level of IL-13 mRNA in lung tissue was positively correlated with the number of eosinophils in BALF and the level of MUC5AC mRNA in lung tissue.
  
  
  CONCLUSIONS
  These findings suggest that increased expression of a single-gene, mCLCA3, could simulate an asthma attack, and its mechanism may involve mCLCA3 overexpression up-regulating IL-13 expression.
authors.affiliation: Department of Respiratory Medicine, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.
authors.forename: Li
authors.initials: L
authors.lastname: Mei
authors.forename: Li
authors.initials: L
authors.lastname: He
authors.forename: Si-Si
authors.initials: SS
authors.lastname: Wu
authors.forename: Bo
authors.initials: B
authors.lastname: Zhang
authors.forename: Yong-Jian
authors.initials: YJ
authors.lastname: Xu
authors.forename: Zhen-Xiang
authors.initials: ZX
authors.lastname: Zhang
authors.forename: Jian-Ping
authors.initials: JP
authors.lastname: Zhao
authors.forename: Hui-Lan
authors.initials: HL
authors.lastname: Zhang
mesh_terms: D000485:Allergens; D000818:Animals; D001249:Asthma; D018118:Chloride Channels; D005260:Female; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism*; D018793:Interleukin-13 / Q000378:metabolism; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism; D015848:Interleukin-5 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D055271:Mucin 5AC / Q000235:genetics / Q000378:metabolism*; D010047:Ovalbumin / Q000494:pharmacology
chemical_list: D000485:Allergens; D018118:Chloride Channels; C115376:ClC-3 channel; D018793:Interleukin-13; D015848:Interleukin-5; C524679:Muc5ac protein, mouse; D055271:Mucin 5AC; D015847:Interleukin-4; D010047:Ovalbumin