肺疾患におけるNOSsの役割の多様性

抄録

We investigated the roles of nitric oxide synthases (NOSs) in the pathogenesis of lung diseases by using our triple n/i/eNOSs^-/- mice. Bleomycin treatment resulted in pulmonary fibrosis (PF) in wild-type (WT), single nNOS^-/-, iNOS^-/-, and eNOS^-/-, and triple n/i/eNOSs^-/- mice as compared with saline treatment. PF was exacerbated only in triple NOSs^-/- mice, but not in any single NOS^-/- mice, as compared with WT mice, suggesting a protective role of NOSs in the development of PF（Respir Res 2014). Hypoxic exposure led to pulmonary hypertension (PH) in all WT, single NOS^-/-, and triple NOSs^-/- mice as compared with normoxic exposure. PH was aggravated in triple NOSs^-/- mice and, to a lesser extent, in single eNOS^-/- mice as compared with WT mice, again suggesting a protective role of NOSs in the development of PH (AJRCCM 2018). In contrast, ovalbumin-induced bronchial asthmatic changes (BA) were markedly mitigated in triple NOSs^-/- than in WT mice, suggesting an opposing injurious role of NOSs in the development of BA（Lung 2016). We recently found that spontaneous development of pulmonary emphysematous changes (PE) was noted only in triple n/i/eNOSs^-/- mice, suggesting a preventive role of NOSs in the development of PE. Taken together, our findings demonstrate diversity of the roles of NOSs in the pathogenesis of lung diseases.