猪胸膜肺炎放线杆菌感染小鼠所致炎症中TLR-4信号通路涉及细胞焦亡

TLR-4 involvement in pyroptosis of mice with pulmonary inflammation infected by Actinobacillus pleuropneumoniae

摘要:

摘要:【目的】探讨革兰氏阴性菌胸膜肺炎放线杆菌(Actinobacillus Pleuropneumoniae，APP)感染小鼠致肺病变的分子细胞机制，以改善猪传染性胸膜肺炎的防治。【方法】滴鼻法感染小鼠，观察肺部眼观病变，石蜡切片HE染色观察肺组织病变。RT-PCR和qPCR方法检测小鼠肺部的Caspase-1、Caspase-3、TNF-α、IL-1β、IL-6、IL-18、TLＲ-4表达量的变化。【结果】小鼠在感染后48h内死亡，解剖后观察小鼠肺部有严重出血和炎症。实验组小鼠肺组织IL-1β、IL-6、IL-18 和TNF-α的表达水平显著增加;TLR-4的表达量显著上调;肺部组织Caspase-1的表达水平明显升高，而Caspase-3的表达水平未见明显变化。【结论】TLR-4信号通路可能参与APP感染引起的肺部炎症的发生，APP感染后激活TLR-4信号通路使有关细胞释放炎症因子，引起的肺部炎症。炎症可能涉及Caspase-1参与的细胞焦亡。

Abstract:

Abstract:［Objective］Pyroptosis is a caspase-1 dependent programmed cell death and involves pathogenesis of infectious diseases by releasing many pro-inflammatory cytokines to induced inflammation．TLR-4 plays an important role in mediating pathogenesis of some infectious diseases． In this study，we detected the expression of TLR-4 and some molecules (e．g caspase-1，TNF-α，IL-1β，IL-6，IL-18) related with pyroptosis to determine its involvement and mechanisms of pulmonary inflammation in mice infected by A．pleuropneumoniae．［Methods］ Mice were intranasally infected by A．pleuropneumoniae and killed 48 hours post infection．Pulmonary gross lesion and histological pathology by H-E were observed． Expression levels of caspase-1，caspase-3，TNF-α，IL-1β，IL-6，IL-18，and TLＲ-4 in lung of mice were detected by RT-PCR and qPCR．［Results］Serious pulmonary hemorrhage and inflammation in infected mice were observed． Expression levels of caspase-1，caspase-3，TNF-α，IL-1β，IL-6，IL-18 and TLR-4 increased，and expression levels of caspase-3 were not changed in lung of infected mice．［Conclusion］ TLＲ-4 might be involved in pulmonary inflammation of mice infected by A．pleuropneumoniae． After induced by activated TLR-4 some cells in this lesion expressed pro-inflammatory cytokines．These cytokines would induce pulmonary inflammation． This lesion might involve pyroptosis with caspase-1 expression．