阻断 GITRL/GITR 信号通路通过抑制 MAPKs 和 NF-κB 信号通路减轻屋尘螨诱导的过敏性哮喘。
Blockade of GITRL/GITR signaling pathway attenuates house dust mite-induced allergic asthma in mice through inhibition of MAPKs and NF-κB signaling.
机构信息
Department of Respiratory Medicine, Children's Hospital of Chongqing Medical University, Chongqing, PR China; National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Children's Hospital of Chongqing Medical University, Chongqing, PR China.
National Clinical Research Center for Child Health and Disorders, Ministry of Education Key Laboratory of Child Development and Disorders, China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Chongqing Key Laboratory of Pediatrics, Children's Hospital of Chongqing Medical University, Chongqing, PR China; Department of Cardiothoracic Surgery, Children's Hospital of Chongqing Medical University, Chongqing, PR China.
出版信息
Mol Immunol. 2021 Sep;137:238-246. doi: 10.1016/j.molimm.2021.07.005. Epub 2021 Jul 20.
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.
GITRL/GITR 信号通路在过敏、炎症、移植和自身免疫中发挥重要作用。然而，其在哮喘中的作用尚不清楚。因此，本研究旨在探讨该通路的变化，并观察其阻断对哮喘的治疗作用。通过使用屋尘螨诱导的哮喘模型，观察 GITRL/GITR 及其下游分子 MAPKs（如 p38 MAPK、JNK 和 Erk）和 NF-κB 的变化。之后，通过重组腺相关病毒敲低小鼠肺部的 GITRL，观察对其下游分子的影响，并评估对哮喘的治疗效果。结果表明，GITRL/GITR 及其下游分子 MAPKs/NF-κB 在哮喘小鼠中被激活。GITRL 敲低后，这种激活被抑制，过敏性气道炎症和气道高反应性减轻。这些结果表明，GITRL/GITR-MAPKs/NF-κB 信号通路参与了哮喘的发病机制。阻断 GITRL/GITR 信号通路在屋尘螨诱导的过敏性哮喘小鼠模型中表现出保护作用。
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