title: Suppression of heme oxygenase-1 activity reduces airway hyperresponsiveness and inflammation in a mouse model of asthma.
abstract: OBJECTIVE
  Carbon monoxide (CO) levels in expired gas are higher in patients with bronchial asthma than in healthy individuals. Heme oxygenase-1 (HO-1) is a rate-limiting enzyme that catalyzes the degradation of heme to yield biliverdin, CO and free iron. Thus, HO-1 is implicated in the pathogenesis of bronchial asthma. However, whether HO-1 expression and activity in lung tissue are related to allergic airway inflammation remains unclear. We investigated whether expression of HO-1 is related to allergic airway inflammation in lungs and whether HO-1 could influence airway hyperresponsiveness and eosinophilia in mice sensitized to ovalbumin (OVA).
  
  
  METHODS
  C57BL/6 mice immunized with OVA were challenged thrice with an aerosol of OVA every second day for 8 days. HO-1-positive cells were identified by immunostaining in lung tissue, and zinc protoporphyrin (Zn-PP), a competitive inhibitor of HO-1, was administered intraperitoneally to OVA-immunized C57BL/6 mice on day 23 (day before inhalation of OVA) and immediately before inhalation on the subsequent 4 days (total five doses). Mice were analyzed for effects of HO-1 on AHR, inflammatory cell infiltration and cytokine levels in lung tissue. Ethical approval was obtained from the concerned institutional review board.
  
  
  RESULTS
  Number of HO-1-positive cells increased in the subepithelium of the bronchi after OVA challenge, and HO-1 localized to alveolar macrophages. Zn-PP clearly inhibited AHR, pulmonary eosinophilia and IL-5 and IL-13 expression in the lung tissue.
  
  
  CONCLUSIONS
  Expression of HO-1 is induced in lung tissue during attacks of allergic bronchial asthma, and its activity likely amplifies and prolongs allergic airway inflammation.
authors.affiliation: a Department of Respiratory Medicine , Hyogo College of Medicine , Nishinomiya , Hyogo , Japan .
authors.forename: Kozo
authors.initials: K
authors.lastname: Kuribayashi
authors.forename: Shin-ichiro
authors.initials: S
authors.lastname: Iida
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Nakajima
authors.forename: Norihiko
authors.initials: N
authors.lastname: Funaguchi
authors.forename: Chiharu
authors.initials: C
authors.lastname: Tabata
authors.forename: Kazuya
authors.initials: K
authors.lastname: Fukuoka
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Fujimori
authors.forename: Daizo
authors.initials: D
authors.lastname: Ihaku
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakano
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001249:Asthma / Q000276:immunology*; D016535:Bronchial Hyperreactivity / Q000276:immunology*; D018791:CD4 Lymphocyte Count; D004195:Disease Models, Animal; D004802:Eosinophilia / Q000276:immunology*; D051547:Heme Oxygenase-1 / Q000096:biosynthesis*; D007249:Inflammation / Q000276:immunology*; D008168:Lung / Q000276:immunology*; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D011524:Protoporphyrins / Q000494:pharmacology
chemical_list: D011524:Protoporphyrins; C017803:zinc protoporphyrin; D010047:Ovalbumin; D051547:Heme Oxygenase-1; D000109:Acetylcholine
keywords: Airway inflammation; HO-1; allergy; lungs; oxidants; zinc protoporphyrin