101. Decreased Bronchial Eosinophilic Inflammation and Mucus Hypersecretion in Asthmatic Mice Lacking All Nitric Oxide Synthase Isoforms
- Author
-
Hiroshi Mukae, Ke Yong Wang, Kazuhiro Yatera, Shingo Noguchi, Nobuyuki Yanagihara, Yumiko Toyohira, Masato Tsutsui, Hiroaki Shimokawa, Takaaki Ogoshi, Kentaro Akata, Takashi Kido, and Keisuke Naito
- Subjects
Pulmonary and Respiratory Medicine ,Chemokine CCL11 ,Male ,Pathophysiology of asthma ,Chemokine ,Gene Expression ,03 medical and health sciences ,Interferon-gamma ,Mice ,0302 clinical medicine ,Medicine ,Animals ,RNA, Messenger ,Bronchitis ,Chemokine CCL2 ,Mice, Knockout ,Lung ,Interleukin-13 ,biology ,business.industry ,Monocyte ,Interleukin ,respiratory system ,Mucus ,Asthma ,respiratory tract diseases ,Interleukin-10 ,Nitric oxide synthase ,Eosinophils ,Mice, Inbred C57BL ,Ovalbumin ,medicine.anatomical_structure ,030228 respiratory system ,030220 oncology & carcinogenesis ,Immunology ,biology.protein ,Cytokines ,Chemokine CCL17 ,Interleukin-4 ,Interleukin-5 ,Nitric Oxide Synthase ,business - Abstract
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(-/-)).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.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.Using asthmatic n/i/eNOS(-/-) mice, NO plays important roles in accelerating bronchial eosinophilic inflammation and mucus hypersecretion in the pathophysiology of asthma.
- Published
- 2015