2. Academic Validation
  3. Toll-Like Receptor 9 Aggravates Pulmonary Fibrosis by Promoting NLRP3-Mediated Pyroptosis of Alveolar Epithelial Cells

Toll-Like Receptor 9 Aggravates Pulmonary Fibrosis by Promoting NLRP3-Mediated Pyroptosis of Alveolar Epithelial Cells

  • Inflammation. 2024 Mar 18. doi: 10.1007/s10753-024-02006-5.
Chunnian Ren 1 2,  Quan Wang 2,  Shulei Fan 3,  Tao Mi 1,  Zhaoxia Zhang 1,  Dawei He 4 5
Affiliations

Affiliations

  • 1 Department of Urology, Children's Hospital of Chongqing Medical University, 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, Chongqing, People's Republic of China.
  • 2 Department of Cardiothoracic Surgery, Children's Hospital of Chongqing Medical University , 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, Chongqing, People's Republic of China.
  • 3 Department of Respiratory Medicine, Second Affiliated Hospital of Chongqing Medical University, Chongqing, China.
  • 4 Department of Urology, Children's Hospital of Chongqing Medical University, 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, Chongqing, People's Republic of China. hedawei@hospital.cqmu.edu.cn.
  • 5 Second Affiliated Hospital of Chongqing Medical University, Chongqing, China. hedawei@hospital.cqmu.edu.cn.
PMID: 38498270 DOI: 10.1007/s10753-024-02006-5
Abstract

The apoptosis-prone property of alveolar epithelial cells plays a crucial role in pulmonary fibrosis(PF), but the role of Pyroptosis in it is still unclear. Toll-like Receptor 9(TLR9) has been reported to play a vital role in the pathogenesis of many diseases. However, the effect of TLR9 on alveolar epithelial cells in PF has not been fully elucidated. Gene expression microarray related to Idiopathic pulmonary fibrosis(IPF) was obtained from the Gene Expression Omnibus(GEO) database. In the mouse model of bleomycin-induced PF, adeno-associated virus(AAV6) was used to interfere with TLR9 to construct TLR9 knockdown mice to study the role of TLR9 in PF, and the specific mechanism was studied by intratracheal instillation of NLR family pyrin domain containing 3(NLRP3) activator. In vitro experiments were performed using A549 cells. Bleomycin-induced Pyroptosis in the lung tissue of PF mice increased, and TLR9 protein levels also increased, especially in alveolar epithelial cells. The levels of fibrosis and Pyroptosis in lung tissue of TLR9 knockdown mice were improved. We found that TLR9 can bind to the NLRP3, thereby increasing the activation of the NLRP3/Caspase-1 inflammasome pathway. When we use the NLRP3 Activator, the levels of fibrosis and Pyroptosis in lung tissue of TLR9 knockout mice can be counteracted. Pyroptosis of alveolar epithelial cells plays a vital role in PF, and TLR9 can promote NLRP3-mediated Pyroptosis of alveolar epithelial cells to aggravate the progression of PF and may become a feasible target for the prevention and treatment of PF.

Keywords

Alveolar epithelial cell; Cell death; Idiopathic pulmonary fibrosis; Pulmonary fibrosis; Pyroptosis.

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