Blockade of GITRL/GITR signaling pathway attenuates house dust mite-induced allergic asthma in mice through inhibition of MAPKs and NF-κB signaling.

Jul 26, 2021

Contributor: Yaping Wang,Bo Liu,Chao Niu,Wenjing Zou,Lili Yang,Ting Wang,Daiyin Tian,Zhengxiu Luo,Jihong Dai,Qubei Li,Enmei Liu,Caihui Gong,Zhou Fu,Fengxia Ding

Blockade of GITRL/GITR signaling pathway attenuates house dust mite-induced allergic asthma in mice through inhibition of MAPKs and NF-κB signaling.

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.
Copyright © 2021. Published by Elsevier Ltd.

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About The Expert

Yaping Wang

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.

Bo Liu

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.

Chao Niu

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.

Wenjing Zou

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.

Lili Yang

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.

Ting Wang

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.

Daiyin Tian

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.

Zhengxiu Luo

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.

Jihong Dai

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.

Qubei Li

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.

Enmei Liu

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.

Caihui Gong

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.

Zhou Fu

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.

Fengxia Ding

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. Electronic address: 482613@hospital.cqmu.edu.cn.

References

PubMed