Pulmonary C-fiber degeneration downregulates IFN-gamma receptor 1 via IFN-alpha induction to attenuate RSV-induced airway hyperresponsiveness
Pulmonary C-fiber degeneration downregulates IFN-gamma receptor 1 via IFN-alpha induction to attenuate RSV-induced airway hyperresponsiveness
复制标题
肺 C 纤维变性通过 IFN-α 诱导下调 IFN-γ 受体 1，以减弱 RSV 诱导的气道高反应性
DOI：
10.1016/j.virol.2017.06.034
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Liu EM
中科院分区：
文献类型：
--
作者：
Ye Zhixu;Ren Luo;Tang Zhengzhen;Ye Zhixu;Tang Zhengzhen;Deng Yu;Xie Xiaohong;Fu Zhou;Luo ZhengXiu;Zang Na;Liu Enmei;Xu Fadi;Zang N;Liu EM
呼吸道合胞病毒（RSV）是婴儿呼吸道感染的主要原因。不幸的是，目前还没有针对RSV的有效疫苗或治疗。肺C纤维（PCF）是调节肺部炎症和气道高反应性（AHR）的关键。我们以前报道IFN-γ部分介导RSV诱导的气道疾病。在本研究中，我们发现PCF变性通过下调IFN-γ受体1（IFNGR 1）减轻RSV诱导的气道炎症，尤其是AHR，但对IFN-γ诱导无影响。相反，PCF变性实际上增加了IFN-α/β水平，STAT 1和磷酸化STAT 1（pSTAT 1）的水平也是如此。外源性IFN-α处理诱导STAT 1活化并下调IFNGR 1表达。这些结果表明，PCF通过诱导IFN-α调节IFN-γ介导的气道炎症和AHR来影响IFNGR 1的表达。因此，靶向PCF激活可能有助于控制RSV诱导的气道疾病，特别是AHR，即使存在炎症。
Respiratory syncytial virus (RSV) is a leading cause of respiratory infection in infants. Unfortunately, no effective vaccine or treatment against RSV is currently available. Pulmonary C-fibers (PCFs) are critical for regulating pulmonary inflammation and airway hyperresponsiveness (AHR). We previously reported that IFN-γ partially mediated RSV-induced airway disorders. In this study, we found that PCF degeneration alleviated RSV-induced airway inflammation, especially AHR by downregulating IFN-γ receptor 1 (IFNGR1), but had no effect on IFN-γ induction. In contrast, PCF degeneration actually increased IFN-α/β levels, as were the levels of STAT1 and phosphorylated STAT1 (pSTAT1). Exogenous IFN-α treatment induced STAT1 activation and downregulated IFNGR1 expression. These results suggest that PCFs affect IFNGR1 expression by inducing IFN-α to regulate IFN-γ-mediated airway inflammation and AHR. Thus, targeting PCFs activation may help control RSV-induced airway disorders, especially AHR, even with the presence of inflammation.