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

作者全名："Ren, Chunnian; Wang, Quan; Fan, Shulei; Mi, Tao; Zhang, Zhaoxia; He, Dawei"

作者地址："[Ren, Chunnian; Mi, Tao; Zhang, Zhaoxia; He, Dawei] Chongqing Med Univ, Natl Clin Res Ctr Child Hlth & Disorders, Minist Educ,Key Lab Child Dev & Disorders,Chongqin, Dept Urol,Childrens Hosp,China Int Sci & Technol C, Chongqing, Peoples R China; [Ren, Chunnian; Wang, Quan] Chongqing Medical Univ, China Int Sci & Technol Cooperat Base Child Dev &, Chongqing Key Lab Pediat,Childrens Hosp,Natl Clin, Minist Educ,Key Lab Child Dev & Disorders,Dept Car, Chongqing, Peoples R China; [Fan, Shulei] Chongqing Med Univ, Affiliated Hosp 2, Dept Resp Med, Chongqing, Peoples R China; [He, Dawei] Chongqing Med Univ, Affiliated Hosp 2, Chongqing, Peoples R China"

通信作者："He, DW (通讯作者)，Chongqing Med Univ, Natl Clin Res Ctr Child Hlth & Disorders, Minist Educ,Key Lab Child Dev & Disorders,Chongqin, Dept Urol,Childrens Hosp,China Int Sci & Technol C, Chongqing, Peoples R China."

来源：INFLAMMATION

ESI学科分类：IMMUNOLOGY

WOS号：WOS:001186100800001

JCR分区：Q2

影响因子：4.5

年份：2024

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期号：　

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文献类型：Article; Early Access

关键词：Idiopathic pulmonary fibrosis; Pulmonary fibrosis; Pyroptosis; Alveolar epithelial cell; Cell death

摘要："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."

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