Decreased airway eosinophilic inflammation, hypersecretion and remodeling in mice lacking all nitric oxide synthase isoforms

Abstract

Background

Nitric oxide synthase (NOS) is a system consists of three isoforms, inducible NOS (iNOS), neuronal NOS (nNOS) and endothelial NOS (eNOS). Several studies have shown that eosinophilic inflammation of the respiratory tract is reduced in asthmatic iNOS-knockout murine model. On the other hand, other studies have shown worsened eosinophilic inflammation in asthmatic murine model administrated iNOS inhibitor. These controversial results may be due to compensatory mechanisms by the rest of other NOS isoforms. To elucidate real role(s) of NO and NOSs in eosinophilic inflammation of bronchial asthma, we used the mice deficient in all NOS isoforms (triply n/i/eNOS(-/-) mice) in this study.

Methods

Wild-type (C57/BL6) mice and triply n/i/eNOS(-/-) mice were sensitized with ovalbumin (OVA) and the adjuvant and then challenged OVA exposure. Pathological and immunohistochemical findings, interleukin (IL) -4, -5 and -13 in the lung tissues were evaluated.

Results

A decrease of eosinophilic inflammation, bronchial secretion and airway remodeling was observed in triply n/i/eNOS(-/-) mice in comparison with wild-type mice. IL-4, IL-5, IL-13 in the lung of triply n/i/eNOS(-/-) mice were significantly reduced compared to wild-type mice.

Conclusion

Using the mice lacking all isoforms of NOS, NO plays an important role in eosinophilic inflammation, hypersecretion and remodeling in the pathogenesis of bronchial asthma.