title: A zinc chelator TPEN attenuates airway hyperresponsiveness and airway inflammation in mice in vivo.
abstract: BACKGROUND
  Zinc is an essential element required for the cell metabolism, including gene transcription, signal transduction, immunity, and apoptosis. The pathophysiological role of zinc in asthma, however, is not entirely clear. Mast cells have been implicated in atopic asthma, and zinc deprivation has been reported to reduce mast cell activation. Here, we investigate the effects of a zinc chelator, N,N,N',N'-tetrakis (2-pyridyl-methyl) ethylenediamine (TPEN), on asthmatic responses in mouse models of ovalbumin (OVA)-induced airway hyperresponsiveness and allergic airway inflammation.
  
  
  METHODS
  Mice were sensitized with OVA with or without the adjuvant aluminum hydroxide (alum) and subjected to OVA exposure with or without treatment of TPEN. Cell profiles and cytokine levels in bronchoalveolar lavage (BAL) fluids, airway responsiveness to inhaled acetylcholine, and goblet cell hyperplasia after allergen exposure were assessed.
  
  
  RESULTS
  In mice sensitized to OVA without alum, TPEN significantly suppressed airway hyperresponsiveness and eosinophilia in BAL fluids. TPEN also attenuated the upregulation of TNFα, IL-13 and IL-4 in BAL fluids and goblet cell hyperplasia after OVA exposure. By contrast, in mice sensitized to OVA with alum, TPEN suppressed eosinophilia in BAL fluids but not airway hyperresponsiveness and goblet cell hyperplasia.
  
  
  CONCLUSIONS
  In pulmonary allergic inflammation induced in mice immunized with antigen without alum, zinc chelator inhibits airway inflammation and hyperresponsiveness. These findings suggest that zinc may be a therapeutic target of allergic asthma.
authors.affiliation: Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Fukuyama
authors.forename: Yuko
authors.initials: Y
authors.lastname: Matsunaga
authors.forename: Wang
authors.initials: W
authors.lastname: Zhanghui
authors.forename: Naotaka
authors.initials: N
authors.lastname: Noda
authors.forename: Yukari
authors.initials: Y
authors.lastname: Asai
authors.forename: Atsushi
authors.initials: A
authors.lastname: Moriwaki
authors.forename: Takafumi
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Takako
authors.initials: T
authors.lastname: Nakano
authors.forename: Koichiro
authors.initials: K
authors.lastname: Matsumoto
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Nakanishi
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Inoue
mesh_terms: D000485:Allergens / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D016535:Bronchial Hyperreactivity / Q000188:drug therapy* / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D002614:Chelating Agents / Q000627:therapeutic use*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004802:Eosinophilia / Q000276:immunology; D005029:Ethylenediamines / Q000627:therapeutic use*; D020397:Goblet Cells / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D006965:Hyperplasia; D007073:Immunoglobulin E / Q000276:immunology; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology; D018793:Interleukin-13 / Q000494:pharmacology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D012137:Respiratory System / Q000187:drug effects / Q000276:immunology; D015032:Zinc / Q000378:metabolism
chemical_list: D000485:Allergens; D002614:Chelating Agents; D016207:Cytokines; D005029:Ethylenediamines; D018793:Interleukin-13; D007073:Immunoglobulin E; D010047:Ovalbumin; D015032:Zinc; C044387:N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine