{"title":"The Dynamic Expression Changes of Neutrophil Extracellular Traps in Mouse Apical Periodontitis: A Potential Correlation With IL-17.","authors":"Zihan Ma, Xiaoyue Sun, Ying Lin, Zijun Wang, Qing Nie, Jingjing Yu, Jingwen Yang, Lingxin Zhu","doi":"10.1155/jimr/8039031","DOIUrl":null,"url":null,"abstract":"<p><p>Neutrophil extracellular traps (NETs) consist of decondensed chromatin and antimicrobial proteins, which are released from neutrophils and have been implicated in several inflammatory diseases. NETs and interleukin (IL)-17 constitute a feed-forward loop that promotes immunopathological development of inflammation. Therefore, this study aimed to investigate the dynamic distribution of NETs and their colocalization with IL-17 during the progression of apical periodontitis in established mouse models. Apical periodontitis was induced in mice by exposing the pulp of the mandibular first molars, with mandibles harvested on day 0, 7, 14, 21, and 28 after pulp exposure. Micro-CT and high-resolution X-ray scanning showed progressive increases in both the area and volume of periapical lesions from day 0 to day 28. Osteoclasts in the periapical lesions were identified using tartrate-resistant acid phosphatase (TRAP) staining, with their numbers peaking on day 21. Immunofluorescence staining was performed for citrullinated histone H3 (CitH3), myeloperoxidase (MPO), neutrophil elastase (NE), and IL-17 to localize NETs and their colocalization with IL-17 in lesions. NETs, which were visible on day 7 and increased gradually until day 21, primarily located in inflammatory infiltration areas of the periapical tissue. Additionally, western blot analysis showed increased CitH3 expression in periapical lesions on day 21 after pulp exposure, further confirming the presence of NETs. Both RT-qPCR and enzyme-linked immunosorbent assay (ELISA) revealed increased IL-17 expression in periapical lesions. The colocalization of CitH3, the major component of NETs and IL-17 peaked on day 21 after pulp exposure. Furthermore, in vitro experiments demonstrated that IL-17 promoted NETs formation under lipopolysaccharide (LPS)-simulated inflammatory conditions. Our findings indicated that NETs expression changed dynamically and suggested a feedback loop between NETs and IL-17 during the development of apical periodontitis in mouse models.</p>","PeriodicalId":15952,"journal":{"name":"Journal of Immunology Research","volume":"2025 ","pages":"8039031"},"PeriodicalIF":3.6000,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12445725/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Immunology Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1155/jimr/8039031","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
引用次数: 0
Abstract
Neutrophil extracellular traps (NETs) consist of decondensed chromatin and antimicrobial proteins, which are released from neutrophils and have been implicated in several inflammatory diseases. NETs and interleukin (IL)-17 constitute a feed-forward loop that promotes immunopathological development of inflammation. Therefore, this study aimed to investigate the dynamic distribution of NETs and their colocalization with IL-17 during the progression of apical periodontitis in established mouse models. Apical periodontitis was induced in mice by exposing the pulp of the mandibular first molars, with mandibles harvested on day 0, 7, 14, 21, and 28 after pulp exposure. Micro-CT and high-resolution X-ray scanning showed progressive increases in both the area and volume of periapical lesions from day 0 to day 28. Osteoclasts in the periapical lesions were identified using tartrate-resistant acid phosphatase (TRAP) staining, with their numbers peaking on day 21. Immunofluorescence staining was performed for citrullinated histone H3 (CitH3), myeloperoxidase (MPO), neutrophil elastase (NE), and IL-17 to localize NETs and their colocalization with IL-17 in lesions. NETs, which were visible on day 7 and increased gradually until day 21, primarily located in inflammatory infiltration areas of the periapical tissue. Additionally, western blot analysis showed increased CitH3 expression in periapical lesions on day 21 after pulp exposure, further confirming the presence of NETs. Both RT-qPCR and enzyme-linked immunosorbent assay (ELISA) revealed increased IL-17 expression in periapical lesions. The colocalization of CitH3, the major component of NETs and IL-17 peaked on day 21 after pulp exposure. Furthermore, in vitro experiments demonstrated that IL-17 promoted NETs formation under lipopolysaccharide (LPS)-simulated inflammatory conditions. Our findings indicated that NETs expression changed dynamically and suggested a feedback loop between NETs and IL-17 during the development of apical periodontitis in mouse models.
期刊介绍:
Journal of Immunology Research is a peer-reviewed, Open Access journal that provides a platform for scientists and clinicians working in different areas of immunology and therapy. The journal publishes research articles, review articles, as well as clinical studies related to classical immunology, molecular immunology, clinical immunology, cancer immunology, transplantation immunology, immune pathology, immunodeficiency, autoimmune diseases, immune disorders, and immunotherapy.