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Decreased Bronchial Eosinophilic Inflammation and Mucus Hypersecretion in Asthmatic Mice Lacking All Nitric Oxide
Kentaro Akata1, Kazuhiro Yatera2, Ke-Yong Wang3
1Department of Respiratory Medicine, University of Occupational and Environmental Health, Japan (UOEH), 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu, Fukuoka, 807-8555, Japan.
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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