LPS aggravates lung inflammation induced by RSV by promoting the ERK-MMP-12 signaling pathway in mice
LPS aggravates lung inflammation induced by RSV by promoting the ERK-MMP-12 signaling pathway in mice
复制标题
LPS通过促进ERK-MMP-12信号通路加重RSV诱导的小鼠肺部炎症
DOI：
10.1186/s12931-020-01453-6
复制
发表时间：
2020-07-21
影响因子：
5.8
通讯作者：
Liu, Enmei
中科院分区：
文献类型：
--
作者：
Chen, Shenglin;Xie, Jun;Liu, Enmei
背景呼吸道合胞病毒可导致持续性呼吸道炎症和气道高反应性(AHR)，并与儿童反复喘息和哮喘密切相关，但其潜在机制尚不清楚。脂多糖(LPS)也与哮喘的发生和加重有关。然而，吸入内毒素是否能增强RSV诱导的呼吸道炎症尚不清楚。在本研究中，我们利用内毒素和呼吸道合胞病毒重叠感染的小鼠模型来探索其潜在的致病机制。方法小鼠在第0天感染RSV，从第35天到第41天接种内毒素，第42天采集标本。测定炎症细胞数、肺组织病理学和AHR。采用ELISA法检测细胞因子，免疫印迹法检测ERK、JNK、p38的表达。MMP408、PD98059、SP600125和SB203580分别抑制MMP12、ERK、JNK和p38的表达。体内抑制MMP12或ERK信号通路均可减轻内毒素诱导的气道炎症和急性呼吸道高反应性反应。结论RSV感染小鼠暴露于内毒素可导致ERK-MMP12表达增强，进而导致肺部炎症和AHR增加。这些发现为现场研究呼吸道合胞病毒后毛细支气管炎后因接触脂多糖而导致的反复喘息提供了新的信息。
BackgroundRSV can lead to persistent airway inflammation and airway hyperresponsiveness (AHR), and is intimately associated with childhood recurrent wheezing and asthma, but the underlying mechanisms remain unclear. Lipopolysaccharide (LPS) is also implicated in the onset and exacerbation of asthma. However, whether inhalation of LPS can boost airway inflammation induced by RSV is not clear. In this study, we utilized an LPS- and RSV-superinfected mouse model to explore underlying pathogenesis.MethodsMice were infected with RSV on day 0 and inoculated with LPS from day 35 to day 41, samples were collected on day 42. Inflammatory cells, lung histopathology and AHR were measured. Cytokines were detected by ELISA and ERK, JNK, p38 was determined by western blot. MMP408, PD98059, SP600125 and SB203580 were used to inhibit MMP-12, ERK, JNK and p38 respectively.ResultsLPS exposure superimposed on RSV-infected lungs could lead to more vigorous cellular influx, lung structures damage, augmented AHR and higher MMP-12 levels. Inhibition of MMP-12 or ERK signaling pathway in vivo both diminished LPS-driven airway inflammation and AHR.ConclusionsExposure to LPS in RSV-infected mice is associated with enhanced increases in ERK-MMP-12 expression that translates into increased lung inflammation and AHR. These findings contribute novel information to the field investigating the onset of post-RSV bronchiolitis recurrent wheezing as a result of LPS exposure.