College of Environment and Resource, Research Center of Environment and Health, Shanxi University, Taiyuan, 030006, Shanxi, People's Republic of China.
Environ Sci Pollut Res Int. 2017 Dec;24(36):27843-27854. doi: 10.1007/s11356-017-0402-7. Epub 2017 Oct 7.
Nitrogen dioxide (NO) is a major air pollutant. Epidemiologic studies have found that NO exposure is associated with an increased risk of asthma. Nevertheless, the potential molecular mechanisms remain unclear. In this study, we investigated the effect of NO inhalation on the occurrence of allergic airway inflammation and its underlying mechanisms. Firstly, male Wistar rats were exposed to 2 and 5 mg/m NO (28 days, 5 h/day). The results showed that NO exposure could induce pulmonary inflammatory response, mucus formation, and Th1/Th2 imbalance in the lung of normal rats, resulting in allergic asthma-like features. Secondly, male Wistar rats were exposed to 5 mg/m NO (42 days, 5 h/day), sensitized with ovalbumin (OVA), challenged with aerosolized OVA, and characterized in asthma models. Results showed that NO exposure aggravated lung inflammation in the OVA-sensitized rats, accompanied by the increase in inflammatory cell infiltration, mucus hypersecretion, and collagen deposition. Furthermore, NO exposure promoted the increase in the expression of mucin gene (MUC5AC) and pro-inflammatory factors [interleukin (IL)-1β, intercellular adhesion molecule-1 (ICAM-1), and IL-6] as well as serum OVA-specific immunoglobulin E (IgE) production. Taken together, we established that NO exposure promotes allergic airway inflammation and increases the asthma susceptibility. The underlying mechanisms involve the promotion of activation of interleukin-4/signal transducer and activator of transcription-6 (IL-4/STAT6) pathway [IL-4 receptor (IL-4R) α, janus kinase (JAK) 1, JAK 3, and STAT6] and related transcription factor [T cell-specific protein-tyrosine kinase (Lck), extracellular-regulated kinase (ERK)1/2, and nuclear factor-κB (NF-κB)]. In particular, the imbalance of Th1/Th2 cell differentiation [IL-4, interferon (IFN)-γ, GATA-binding protein-3 (GATA-3), and T-box expressed in T cells (T-bet)] plays a pivotal role in NO-induced inflammatory responses. These findings may provide a better understanding of mechanism of NO-associated respiratory diseases.
二氧化氮（NO）是一种主要的空气污染物。流行病学研究发现，NO 暴露与哮喘风险增加有关。然而，潜在的分子机制仍不清楚。在这项研究中，我们研究了 NO 吸入对过敏性气道炎症发生的影响及其潜在机制。首先，雄性 Wistar 大鼠暴露于 2 和 5mg/m3 的 NO（28 天，每天 5 小时）。结果表明，NO 暴露可诱导正常大鼠肺部炎症反应、黏液形成和 Th1/Th2 失衡，导致类似哮喘的特征。其次，雄性 Wistar 大鼠暴露于 5mg/m3 的 NO（42 天，每天 5 小时），用卵清蛋白（OVA）致敏，用雾化 OVA 攻击，并在哮喘模型中进行特征描述。结果表明，NO 暴露加重了 OVA 致敏大鼠的肺部炎症，伴有炎症细胞浸润、黏液分泌过度和胶原沉积增加。此外，NO 暴露促进粘蛋白基因（MUC5AC）和促炎因子[白细胞介素（IL）-1β、细胞间黏附分子-1（ICAM-1）和 IL-6]以及血清 OVA 特异性免疫球蛋白 E（IgE）产生的增加。总之，我们建立了 NO 暴露促进过敏性气道炎症并增加哮喘易感性。潜在机制涉及促进白细胞介素-4/信号转导和转录激活因子-6（IL-4/STAT6）途径[白细胞介素-4 受体（IL-4R）α、Janus 激酶（JAK）1、JAK3 和 STAT6]和相关转录因子[T 细胞特异性蛋白酪氨酸激酶（Lck）、细胞外调节激酶（ERK）1/2 和核因子-κB（NF-κB）]的激活。特别是 Th1/Th2 细胞分化失衡[白细胞介素-4、干扰素（IFN）-γ、GATA 结合蛋白-3（GATA-3）和 T 细胞表达的 T 盒（T-bet）]在 NO 诱导的炎症反应中起着关键作用。这些发现可能为更好地理解与 NO 相关的呼吸道疾病的机制提供依据。
