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.

CONCLUSION:

Using asthmatic n/i/eNOS(-/-) mice, NO plays important roles in accelerating bronchial eosinophilic inflammation and mucus hypersecretion in the pathophysiology of asthma.

• Authors: Kentaro Akata, Kazuhiro Yatera, Ke-Yong Wang, Keisuke Naito, Takaaki Ogoshi, Shingo Noguchi, Takashi Kido, Yumiko Toyohira, Hiroaki Shimokawa, Nobuyuki Yanagihara, Masato Tsutsui, Hiroshi Mukae
• Journal: Lung (Lung) Vol. 194 Issue 1 Pg. 121-4 (Feb 2016) ISSN: 1432-1750 [Electronic] United States
• PMID: 26685897 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Ccl17 protein, mouse
• Chemokine CCL11
• Chemokine CCL17
• Chemokine CCL2
• Cytokines
• Interleukin-13
• Interleukin-5
• RNA, Messenger
• Interleukin-10
• Interleukin-4
• Interferon-gamma
• Nitric Oxide Synthase

Topics

• Animals
• Asthma (enzymology, genetics, pathology)
• Bronchitis (immunology, pathology)
• Chemokine CCL11 (genetics)
• Chemokine CCL17 (genetics)
• Chemokine CCL2 (genetics)
• Cytokines (genetics)
• Eosinophils (immunology)
• Gene Expression
• Interferon-gamma (genetics)
• Interleukin-10 (genetics)
• Interleukin-13 (genetics)
• Interleukin-4 (genetics)
• Interleukin-5 (genetics)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Mucus (metabolism)
• Nitric Oxide Synthase (deficiency, genetics)
• RNA, Messenger (analysis)