title: Decreased Bronchial Eosinophilic Inflammation and Mucus Hypersecretion in Asthmatic Mice Lacking All Nitric Oxide Synthase Isoforms.
abstract: BACKGROUND
  Asthma is characterized by airflow limitation with chronic airway inflammation, hyperresponsiveness and mucus hypersecretion. NO is generated by three nitric oxide synthase (i/n/eNOSs) isoforms, but conflicting results have been reported using asthmatic mice treated with NOSs inhibitors and NOS-knockout mice. To elucidate the authentic role of NO/NOSs in asthma, we used asthmatic mice lacking all NOSs (n/i/eNOS(-/-)).
  
  
  METHODS
  Wild-type and n/i/eNOS(-/-) mice were sensitized and challenged with ovalbumin. Pathological findings and expressions of interferon (IFN)-γ, interleukin (IL)-4, -5, -10, -13 and chemokines in the lung were evaluated.
  
  
  RESULTS
  Decreased eosinophilic inflammation, bronchial thickening and mucus secretion, IL-4, -5 and -13, monocyte chemoattractant protein-1, eotaxin-1 and thymus and activation-regulated chemokine expressions were observed in n/i/eNOS(-/-) mice compared to wild-type, but expressions of IFN-γ and IL-10 were similar.
  
  
  CONCLUSIONS
  Using asthmatic n/i/eNOS(-/-) mice, NO plays important roles in accelerating bronchial eosinophilic inflammation and mucus hypersecretion in the pathophysiology of asthma.
authors.affiliation: Department of Respiratory Medicine, University of Occupational and Environmental Health, Japan (UOEH), 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, Fukuoka, 807-8555, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Akata
authors.affiliation: Department of Respiratory Medicine, University of Occupational and Environmental Health, Japan (UOEH), 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, Fukuoka, 807-8555, Japan. yatera@med.uoeh-u.ac.jp.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Yatera
authors.affiliation: Shared-Use Research Center, UOEH, Kitakyushu, Japan.
authors.forename: Ke-Yong
authors.initials: KY
authors.lastname: Wang
authors.affiliation: Department of Respiratory Medicine, University of Occupational and Environmental Health, Japan (UOEH), 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, Fukuoka, 807-8555, Japan.
authors.forename: Keisuke
authors.initials: K
authors.lastname: Naito
authors.affiliation: Department of Respiratory Medicine, University of Occupational and Environmental Health, Japan (UOEH), 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, Fukuoka, 807-8555, Japan.
authors.forename: Takaaki
authors.initials: T
authors.lastname: Ogoshi
authors.affiliation: Department of Respiratory Medicine, University of Occupational and Environmental Health, Japan (UOEH), 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, Fukuoka, 807-8555, Japan.
authors.forename: Shingo
authors.initials: S
authors.lastname: Noguchi
authors.affiliation: Department of Respiratory Medicine, University of Occupational and Environmental Health, Japan (UOEH), 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, Fukuoka, 807-8555, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kido
authors.affiliation: Department of Pharmacology, School of Medicine, UOEH, Kitakyushu, Japan.
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Toyohira
authors.affiliation: Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Shimokawa
authors.affiliation: Department of Pharmacology, School of Medicine, UOEH, Kitakyushu, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Yanagihara
authors.affiliation: Department of Pharmacology, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Tsutsui
authors.affiliation: Department of Respiratory Medicine, University of Occupational and Environmental Health, Japan (UOEH), 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, Fukuoka, 807-8555, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mukae
mesh_terms: D000818:Animals; D001249:Asthma / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D001991:Bronchitis / Q000276:immunology / Q000473:pathology*; D054413:Chemokine CCL11 / Q000235:genetics; D054414:Chemokine CCL17 / Q000235:genetics; D018932:Chemokine CCL2 / Q000235:genetics; D016207:Cytokines / Q000235:genetics*; D004804:Eosinophils / Q000276:immunology; D015870:Gene Expression; D007371:Interferon-gamma / Q000235:genetics; D016753:Interleukin-10 / Q000235:genetics; D018793:Interleukin-13 / Q000235:genetics; D015847:Interleukin-4 / Q000235:genetics; D015848:Interleukin-5 / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009093:Mucus / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000172:deficiency* / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis*
chemical_list: C499538:Ccl17 protein, mouse; D054413:Chemokine CCL11; D054414:Chemokine CCL17; D018932:Chemokine CCL2; D016207:Cytokines; D018793:Interleukin-13; D015848:Interleukin-5; D012333:RNA, Messenger; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase
keywords: Bronchial asthma; Eosinophilic inflammation; Nitric oxide; Nitric oxide synthase