{"title":"通过 miR-182-5p/TLR4 轴,KLF5 介导的气道上皮细胞热解导致哮喘小鼠的气道炎症","authors":"Zhi Lin , Rong Bao , Yang Niu , Xiaomei Kong","doi":"10.1016/j.molimm.2024.03.007","DOIUrl":null,"url":null,"abstract":"<div><p>Asthma is viewed as an airway disease and an inflammatory condition. This study aims to reveal the role of Kruppel-like factor 5 (KLF5)-mediated pyroptosis of airway epithelial cells in airway inflammation in asthma. The asthmatic mouse model was established. The mice were infected with the lentivirus containing sh-KLF5, antagomiR-182–5p, and pc-Toll-like receptor 4 (TLR4). Airway hyperresponsiveness was measured, and the cells in bronchoalveolar lavage fluid (BALF) were sorted and counted. The expression levels of interleukin (IL)-4/IL-13/IL-6/IL-18/IL-1β/NOD-like receptor family pyrin domain containing 3 (NLRP3)/N-gasdermin D (GSDMD-N)/cleaved caspase-1 were detected. The pathological changes in lung tissue were observed. The enrichment of KLF5 in the miR-182–5p promoter region was measured. The binding relationship among KLF5, miR-182–5p, and TLR4 were analyzed. KLF5 was highly expressed in asthmatic mice. Silencing KLF5 improved airway resistance and lung dynamic compliance, reduced the cells in BALF and the expression of IL-4/IL-13/IL-6/NLRP3/GSDMD-N/cleaved caspase-1/IL-18/IL-1β, and alleviated the pathological changes. Mechanistically, KLF5 bonded to the miR-182–5p promoter to inhibit miR-182–5p expression, and miR-182–5p inhibited TLR4. Silencing miR-182–5p or TLR4 overexpression reversed the improvement of silencing KLF5 on airway inflammation and pyroptosis in asthmatic mice. In conclusion, KLF5 inhibited miR-182–5p to promote TLR4 expression, thus aggravating pyroptosis and airway inflammation in asthmatic mice.</p></div>","PeriodicalId":18938,"journal":{"name":"Molecular immunology","volume":null,"pages":null},"PeriodicalIF":3.2000,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"KLF5-mediated pyroptosis of airway epithelial cells leads to airway inflammation in asthmatic mice through the miR-182–5p/TLR4 axis\",\"authors\":\"Zhi Lin , Rong Bao , Yang Niu , Xiaomei Kong\",\"doi\":\"10.1016/j.molimm.2024.03.007\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Asthma is viewed as an airway disease and an inflammatory condition. This study aims to reveal the role of Kruppel-like factor 5 (KLF5)-mediated pyroptosis of airway epithelial cells in airway inflammation in asthma. The asthmatic mouse model was established. The mice were infected with the lentivirus containing sh-KLF5, antagomiR-182–5p, and pc-Toll-like receptor 4 (TLR4). Airway hyperresponsiveness was measured, and the cells in bronchoalveolar lavage fluid (BALF) were sorted and counted. The expression levels of interleukin (IL)-4/IL-13/IL-6/IL-18/IL-1β/NOD-like receptor family pyrin domain containing 3 (NLRP3)/N-gasdermin D (GSDMD-N)/cleaved caspase-1 were detected. The pathological changes in lung tissue were observed. The enrichment of KLF5 in the miR-182–5p promoter region was measured. The binding relationship among KLF5, miR-182–5p, and TLR4 were analyzed. KLF5 was highly expressed in asthmatic mice. Silencing KLF5 improved airway resistance and lung dynamic compliance, reduced the cells in BALF and the expression of IL-4/IL-13/IL-6/NLRP3/GSDMD-N/cleaved caspase-1/IL-18/IL-1β, and alleviated the pathological changes. Mechanistically, KLF5 bonded to the miR-182–5p promoter to inhibit miR-182–5p expression, and miR-182–5p inhibited TLR4. Silencing miR-182–5p or TLR4 overexpression reversed the improvement of silencing KLF5 on airway inflammation and pyroptosis in asthmatic mice. In conclusion, KLF5 inhibited miR-182–5p to promote TLR4 expression, thus aggravating pyroptosis and airway inflammation in asthmatic mice.</p></div>\",\"PeriodicalId\":18938,\"journal\":{\"name\":\"Molecular immunology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.2000,\"publicationDate\":\"2024-04-09\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Molecular immunology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0161589024000609\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular immunology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0161589024000609","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
KLF5-mediated pyroptosis of airway epithelial cells leads to airway inflammation in asthmatic mice through the miR-182–5p/TLR4 axis
Asthma is viewed as an airway disease and an inflammatory condition. This study aims to reveal the role of Kruppel-like factor 5 (KLF5)-mediated pyroptosis of airway epithelial cells in airway inflammation in asthma. The asthmatic mouse model was established. The mice were infected with the lentivirus containing sh-KLF5, antagomiR-182–5p, and pc-Toll-like receptor 4 (TLR4). Airway hyperresponsiveness was measured, and the cells in bronchoalveolar lavage fluid (BALF) were sorted and counted. The expression levels of interleukin (IL)-4/IL-13/IL-6/IL-18/IL-1β/NOD-like receptor family pyrin domain containing 3 (NLRP3)/N-gasdermin D (GSDMD-N)/cleaved caspase-1 were detected. The pathological changes in lung tissue were observed. The enrichment of KLF5 in the miR-182–5p promoter region was measured. The binding relationship among KLF5, miR-182–5p, and TLR4 were analyzed. KLF5 was highly expressed in asthmatic mice. Silencing KLF5 improved airway resistance and lung dynamic compliance, reduced the cells in BALF and the expression of IL-4/IL-13/IL-6/NLRP3/GSDMD-N/cleaved caspase-1/IL-18/IL-1β, and alleviated the pathological changes. Mechanistically, KLF5 bonded to the miR-182–5p promoter to inhibit miR-182–5p expression, and miR-182–5p inhibited TLR4. Silencing miR-182–5p or TLR4 overexpression reversed the improvement of silencing KLF5 on airway inflammation and pyroptosis in asthmatic mice. In conclusion, KLF5 inhibited miR-182–5p to promote TLR4 expression, thus aggravating pyroptosis and airway inflammation in asthmatic mice.
期刊介绍:
Molecular Immunology publishes original articles, reviews and commentaries on all areas of immunology, with a particular focus on description of cellular, biochemical or genetic mechanisms underlying immunological phenomena. Studies on all model organisms, from invertebrates to humans, are suitable. Examples include, but are not restricted to:
Infection, autoimmunity, transplantation, immunodeficiencies, inflammation and tumor immunology
Mechanisms of induction, regulation and termination of innate and adaptive immunity
Intercellular communication, cooperation and regulation
Intracellular mechanisms of immunity (endocytosis, protein trafficking, pathogen recognition, antigen presentation, etc)
Mechanisms of action of the cells and molecules of the immune system
Structural analysis
Development of the immune system
Comparative immunology and evolution of the immune system
"Omics" studies and bioinformatics
Vaccines, biotechnology and therapeutic manipulation of the immune system (therapeutic antibodies, cytokines, cellular therapies, etc)
Technical developments.