Blockade of GITRL/GITR signaling pathway attenuates house dust mite-induced allergic asthma in mice through inhibition of MAPKs and NF-κB signaling
Blockade of GITRL/GITR signaling pathway attenuates house dust mite-induced allergic asthma in mice through inhibition of MAPKs and NF-κB signaling
复制标题
阻断 GITRL/GITR 信号通路可通过抑制 MAPK 和 NF-κB 信号减弱屋尘螨诱发的小鼠过敏性哮喘
作者：
王亚苹;刘博;牛超;邹文静;杨丽丽;王婷;田代印;罗征秀;代继宏;李渠北;刘恩梅;龚财慧;符州;丁凤霞
GITRL/GITR信号通路在变态反应、炎症、移植和自身免疫中发挥重要作用。然而，它在哮喘中的作用仍不清楚。因此，本研究旨在研究该通路的变化，并观察其阻断对哮喘的治疗作用。采用尘螨哮喘模型，观察GITRL/GITR及其下游分子MAPKs(如p38MAPK、JNK、ERK)和核因子κB的变化。用重组腺相关病毒敲除小鼠肺组织中的GITRL，观察其对其下游分子的影响，评价其对哮喘的治疗作用。这些结果表明哮喘小鼠GITRL/GITR及其下游分子MAPKs/NF-κB被激活。GITRL基因敲除后，这种激活被抑制，过敏性气道炎症和气道高反应性得到缓解。这些结果表明GITRL/GITR-MAPKs/NF-κB信号通路参与了哮喘的发病过程。阻断GITRL/GITR信号通路对屋尘螨致过敏性哮喘小鼠模型有保护作用。
GITRL/GITR signaling pathway plays an important role in allergy, inflammation, transplantation and autoimmunity. However, its role in asthma remains unclear. Thus, the present study aimed to investigate changes in this pathway and observe the therapeutic effect of its blocking on asthma. By using house dust mite-induced asthma model, changes of GITRL/GITR and its downstream molecules MAPKs (e.g., p38 MAPK, JNK and Erk) and NF-κB were observed. After that, GITRL in lung of mice was knocked down by recombinant adeno-associated virus to observe the impact on its downstream molecules and assess the therapeutic effect on asthma. These results showed that GITRL/GITR and its downstream molecules MAPKs/NF-κB were activated in asthmatic mice. This activation was suppressed after GITRL knockdown, and allergic airway inflammation and airway hyperresponsiveness were alleviated. These results demonstrate that GITRL/GITR-MAPKs/NF-κB signaling pathway participates in the pathogenesis of asthma. Blockade of GITRL/GITR signaling pathway exhibits protective effects in a mouse model of house dust mite-induced allergic asthma.