Kentaro Akata1, Kazuhiro Yatera2, Ke-Yong Wang3, Keisuke Naito1, Takaaki Ogoshi1, Shingo Noguchi1, Takashi Kido1, Yumiko Toyohira4, Hiroaki Shimokawa5, Nobuyuki Yanagihara4, Masato Tsutsui6, Hiroshi Mukae1. 1. Department of Respiratory Medicine, University of Occupational and Environmental Health, Japan (UOEH), 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, Fukuoka, 807-8555, Japan. 2. 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. 3. Shared-Use Research Center, UOEH, Kitakyushu, Japan. 4. Department of Pharmacology, School of Medicine, UOEH, Kitakyushu, Japan. 5. Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, Sendai, Japan. 6. Department of Pharmacology, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan.
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. CONCLUSION: Using asthmatic n/i/eNOS(-/-) mice, NO plays important roles in accelerating bronchial eosinophilic inflammation and mucus hypersecretion in the pathophysiology of asthma.
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. CONCLUSION: Using asthmatic n/i/eNOS(-/-) mice, NO plays important roles in accelerating bronchial eosinophilic inflammation and mucus hypersecretion in the pathophysiology of asthma.
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