A zinc chelator TPEN attenuates airway hyperresponsiveness and airway inflammation in mice in vivo

Satoru Fukuyama, Yuko Matsunaga, Wang Zhanghui, Naotaka Noda, Yukari Asai, Atsushi Moriwaki, Takafumi Matsumoto, Takako Nakano, Koichiro Matsumoto, Yoichi Nakanishi, Hiromasa Inoue

Research output: Contribution to journalArticlepeer-review

14 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)259-266
Number of pages8
JournalAllergology International
Volume60
Issue number3
DOIs
Publication statusPublished - 2011

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy

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