PDF(Pubmed)
Abstract：
N-acetylcysteine (NAC) is a mucolytic agent with antioxidant and anti-inflammatory properties. The respiratory syncytial virus (RSV) is one of the most important etiological factors of lower respiratory tract infections, and exposure to air pollution appears to be additionally associated with higher RSV incidence and disease severity. We aimed to systematically review the existing literature to determine which molecular mechanisms mediate the effects of NAC in an RSV infection and air pollution, and to identify the knowledge gaps in this field. A search for original studies was carried out in three databases and a calibrated extraction grid was used to extract data on the NAC treatment (dose, timing), the air pollutant type, and the most significant mechanisms. We identified only 28 studies conducted in human cellular models (n = 18), animal models (n = 7), and mixed models (n = 3). NAC treatment improves the barrier function of the epithelium damaged by RSV and air pollution, and reduces the epithelial permeability, protecting against viral entry. NAC may also block RSV-activated phosphorylation of the epidermal growth factor receptor (EGFR), which promotes endocytosis and facilitates cell entry. EGFR also enhances the release of a mucin gene, MUC5AC, which increases mucus viscosity and causes goblet cell metaplasia; the effects are abrogated by NAC. NAC blocks virus release from the infected cells, attenuates the cigarette smoke-induced shift from necrosis to apoptosis, and reverses the block in IFN-γ-induced antiviral gene expression caused by the inhibited Stat1 phosphorylation. Increased synthesis of pro-inflammatory cytokines and chemokines is induced by both RSV and air pollutants and is mediated by the nuclear factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways that are activated in response to oxidative stress. MCP-1 (monocyte chemoattractant protein-1) and RANTES (regulated upon activation, expressed and secreted by normal T cells) partially mediate airway hyperresponsiveness (AHR), and therapeutic (but not preventive) NAC administration reduces the inflammatory response and has been shown to reduce ozone-induced AHR. Oxidative stress-induced DNA damage and cellular senescence, observed during RSV infection and exposure to air pollution, can be partially reversed by NAC administration, while data on the emphysema formation are disputed. The review identified potential common molecular mechanisms of interest that are affected by NAC and may alleviate both the RSV infection and the effects of air pollution. Data are limited and gaps in knowledge include the optimal timing or dosage of NAC administration, therefore future studies should clarify these uncertainties and verify its practical use.
摘要：
N-乙酰半胱氨酸（NAC）是一种具有抗氧化和抗炎特性的粘液溶解剂。呼吸道合胞病毒(RSV)是下呼吸道感染的重要病因之一。暴露于空气污染似乎还与更高的RSV发病率和疾病严重程度相关。我们旨在系统地回顾现有文献，以确定哪些分子机制介导NAC在RSV感染和空气污染中的作用。并确定该领域的知识差距。在三个数据库中进行了原始研究的搜索，并使用校准的提取网格来提取NAC治疗的数据（剂量，定时)，空气污染物类型，和最重要的机制。我们仅确定了28项在人类细胞模型中进行的研究（n=18），动物模型（n=7），和混合模型(n=3)。NAC治疗改善了RSV和空气污染损伤的上皮的屏障功能，并降低上皮通透性，防止病毒进入。NAC还可以阻断RSV激活的表皮生长因子受体（EGFR）的磷酸化，促进内吞作用并促进细胞进入。EGFR还增强了粘蛋白基因的释放，MUC5AC,增加粘液粘度并引起杯状细胞化生；NAC消除了这种影响。NAC阻止病毒从感染细胞中释放,减弱香烟烟雾诱导的从坏死到凋亡的转变，并逆转了由抑制的Stat1磷酸化引起的IFN-γ诱导的抗病毒基因表达的阻断。RSV和空气污染物均可诱导促炎细胞因子和趋化因子的合成增加，并由响应于氧化应激而激活的核因子κB（NF-κB）和丝裂原活化蛋白激酶（MAPK）信号通路介导。MCP-1（单核细胞趋化蛋白-1）和RANTES（在激活时调节，由正常T细胞表达和分泌）部分介导气道高反应性（AHR），和治疗性（但非预防性）NAC给药可减少炎症反应，并已显示可减少臭氧诱导的AHR。氧化应激诱导的DNA损伤和细胞衰老,在RSV感染和暴露于空气污染期间观察到，可以通过NAC管理部分逆转，虽然肺气肿形成的数据存在争议。该综述确定了受NAC影响的潜在常见分子机制，并可能减轻RSV感染和空气污染的影响。数据有限，知识空白包括NAC给药的最佳时机或剂量，因此，未来的研究应该澄清这些不确定性，并验证其实际用途。
