Ricciardolo Fabio L M, Nijkamp Frans P, Folkerts Gert
Unit of Pneumology, IRCCS Gaslini Institute, Genoa, Italy.
Curr Drug Targets. 2006 Jun;7(6):721-35. doi: 10.2174/138945006777435290.
In the respiratory tract, NO is produced by residential and inflammatory cells. NO is generated via oxidation of L-arginine that is catalysed by the enzyme NO synthase (NOS). NOS exists in three distinct isoforms: neuronal NOS (nNOS), inducible NOS (iNOS), and endothelial NOS (eNOS). NO derived from the constitutive isoforms of NOS (nNOS and eNOS) and other NO-adduct molecules (nitrosothiols) are able to modulate bronchomotor tone. NO derived from the inducible isoform of NO synthase, up-regulated by different cytokines via NF-kappaB-dependent pathway, seems to be a pro-inflammatory mediator with immunomodulatory effects. The production of NO under oxidative stress conditions secondarily generates strong oxidising agents (reactive nitrogen species) that may amplify the inflammatory response in asthma and COPD. Moreover, NO can be exhaled and levels are abnormal in stable atopic asthma and during exacerbations in both asthma and COPD. Exhaled NO might therefore be a non-invasive tool to monitor the underlying inflammatory process. It is suggested that NOS regulation provides a novel target in the prevention and treatment of chronic inflammatory diseases of the airways such as asthma and COPD.
在呼吸道中，一氧化氮（NO）由驻留细胞和炎症细胞产生。NO通过一氧化氮合酶（NOS）催化的L-精氨酸氧化生成。NOS存在三种不同的同工型：神经元型NOS（nNOS）、诱导型NOS（iNOS）和内皮型NOS（eNOS）。源自NOS组成型同工型（nNOS和eNOS）的NO以及其他NO加合物分子（亚硝基硫醇）能够调节支气管运动张力。源自诱导型一氧化氮合酶同工型的NO，通过不同细胞因子经NF-κB依赖性途径上调，似乎是一种具有免疫调节作用的促炎介质。氧化应激条件下NO的产生继而生成强氧化剂（活性氮物种），这可能会放大哮喘和慢性阻塞性肺疾病（COPD）中的炎症反应。此外，NO可以呼出，在稳定的特应性哮喘以及哮喘和COPD发作期间其水平异常。因此，呼出的NO可能是监测潜在炎症过程的一种非侵入性工具。有人提出，NOS调节为预防和治疗哮喘和COPD等气道慢性炎症性疾病提供了一个新靶点。
