{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T15:57:56Z","timestamp":1753891076298,"version":"3.41.2"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T00:00:00Z","timestamp":1746489600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Changes in oral neutrophil number and function may occur in patients after orthodontic treatment, affecting the oral immune microenvironment. However, the specific mechanisms are unclear. In this study, we describe the changes in the levels of neutrophil extracellular traps (NET) markers and inflammatory factors in the gingival crevicular fluid (GCF) and saliva of patients after orthodontic treatment and further explore the correlation between them.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>68 patients underwent fixed orthodontic treatment in the Department of Orthodontics from January 2021 to June 2023 were selected. GCF and saliva samples were collected from the patients 1 day before orthodontic treatment and 2 h, 24 h, and 1 week after orthodontic treatment to evaluate changes in NET marker and inflammatory factors. The differences in and associations between NET markers and inflammatory cytokine levels in the GCF and saliva of patients were evaluated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>After fixed orthodontic treatment, the neutrophil elastase (NE), myeloperoxidase (MPO), citrullinated histone 3 (CitH3), and MPO-DNA in the GCF and saliva of the patients increased gradually, the interleukin (IL)-1\u03b2 and IL-8 in the GCF increased gradually, and there were significant differences among the different time points (P&amp;lt;0.05). There was a positive correlation between the NE, MPO, CitH3, MPO-DNA, IL-1\u03b2 and IL-8 in the GCF of patients at 2 hours and 24 hours after orthodontic treatment (P&amp;lt;0.05). There was a significant positive correlation between the GCF and saliva levels of NE, MPO, CitH3, MPO-DNA, IL-1\u03b2 and IL-8 (P&amp;lt;0.05); however, there was no statistically sex- or age-dependent differences in the NE, MPO, CitH3, MPO-DNA, IL-1\u03b2 and IL-8 levels in the GCF of orthodontic patients (P&amp;gt;0.05).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study significantly reveals that NET marker levels in the GCF and saliva rapidly change following the initial orthodontic arch wire stress. The inflammation in periodontal tissues induced by orthodontic stress has the potential to trigger oral inflammation via the GCF. These findings are crucial for understanding the oral immune microenvironment changes during orthodontic treatment, providing a theoretical basis for preventing and treating orthodontic - related periodontal complications, thus having important implications for improving orthodontic treatment outcomes.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1490637","type":"journal-article","created":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T05:26:08Z","timestamp":1746509168000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Characterization and correlation analysis of oral NET markers and inflammatory factor levels in patients after orthodontic treatment: a pilot study"],"prefix":"10.3389","volume":"16","author":[{"given":"Qian","family":"Liu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Axian","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donghui","family":"Guo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Houzhuo","family":"Luo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shishu","family":"Fang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhixin","family":"Song","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Wen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fang","family":"Jin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,5,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.csbj.2021.06.012","article-title":"Staphylococcus aureus induces neutrophil extracellular traps (NETs) and neutralizes their bactericidal potential","volume":"19","author":"Pietro","year":"2021","journal-title":"Comput Struct Biotechnol J"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.it.2019.04.012","article-title":"Neutrophil diversity in health and disease","volume":"40","author":"Carlos","year":"2019","journal-title":"Trends Immunol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"77","DOI":"10.2186\/jpr.JPR_D_21_00238","article-title":"Cyclic pressure-induced cytokines from gingival fibroblasts stimulate osteoclast activity: Clinical implications for alveolar bone loss in denture wearers","volume":"67","author":"Akashi","year":"2023","journal-title":"J prosthodontic Res"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2015.00214","article-title":"Chemokine function in periodontal disease and oral cavity cancer","volume":"6","author":"Sahingur","year":"2015","journal-title":"Front Immunol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1208","DOI":"10.3390\/molecules26051208","article-title":"Gingival crevicular fluid (GCF): A diagnostic tool for the detection of periodontal health and diseases","volume":"26","author":"Fatima","year":"2021","journal-title":"Molecules (Basel Switzerland)"},{"key":"B6","doi-asserted-by":"publisher","first-page":"9949047","DOI":"10.1155\/2023\/9949047","article-title":"Meta-analysis of assessment of total oxidative stress and total antioxidant capacity in patients with periodontitis","volume":"2023","author":"Mohideen","year":"2023","journal-title":"Dis Markers"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1007\/s11914-023-00774-x","article-title":"Osteoimmunology in periodontitis and orthodontic tooth movement","volume":"21","author":"Bushra","year":"2023","journal-title":"Curr Osteoporos Rep"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1038\/s12276-024-01219-w","article-title":"Neutrophils and neutrophil extracellular traps in oral health and disease","volume":"56","author":"Kim","year":"2024","journal-title":"Exp Mol Med"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2021.639144","article-title":"The role of neutrophil extracellular traps in periodontitis","volume":"11","author":"Wang","year":"2021","journal-title":"Front Cell infection Microbiol"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2018-11-844530","article-title":"Neutrophils and NETs in modulating acute and chronic inflammation","volume":"133","author":"C. Fernanda","year":"2019","journal-title":"Blood"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1111\/cpr.13428","article-title":"Epigenetic regulation of chemokine (CC-motif) ligand 2 in inflammatory diseases","volume":"56","author":"Yingyi","year":"2023","journal-title":"Cell Prolif"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1002\/JLB.3RU0620-375R","article-title":"The vitals of NETs","volume":"110","author":"Chuyi","year":"2020","journal-title":"J Leukoc Biol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0765.2010.01288.x","article-title":"Disruption of periodontal integrity induces expression of apin by epithelial cell rests of Malassez","volume":"45","author":"Nishio","year":"2010","journal-title":"J periodontal Res"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajodo.2014.04.015","article-title":"Myeloperoxidase enzymatic activity is increased in patients with different levels of dental crowding after initial orthodontic activation","volume":"146","author":"Navarro-Palacios","year":"2014","journal-title":"Am J orthodontics dentofacial orthopedics: Off Publ Am Assoc Orthodontists its constituent societies Am Board Orthodontics"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1038\/s41577-022-00761-w","article-title":"Tuning immunity through tissue mechanotransduction","volume":"23","author":"Huixun","year":"2022","journal-title":"Nat Rev Immunol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1002\/ctm2.1170","article-title":"Neutrophil, neutrophil extracellular traps and endothelial cell dysfunction in sepsis","volume":"13","author":"Hao","year":"2023","journal-title":"Clin Transl Med"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1080\/14653125.2017.1350329","article-title":"An evaluation and comparison of myeloperoxidase enzymatic activity during initial orthodontic alignment: an in vivo study","volume":"44","author":"Asma","year":"2017","journal-title":"J Orthod"},{"key":"B18","article-title":"Progress in mechanism of formation of neutrophil extracellular traps: Review","volume":"36","author":"Kegong","year":"2020","journal-title":"Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-89390-7_7","article-title":"Inflammasome and oral diseases","volume":"108","author":"Pedro","year":"2018","journal-title":"Exp Suppl"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajodo.2010.01.029","article-title":"Myeloperoxidase activity is increased in gingival crevicular fluid and whole saliva after fixed orthodontic appliance activation","volume":"138","author":"M. Andrea","year":"2010","journal-title":"Am J orthodontics dentofacial orthopedics: Off Publ Am Assoc Orthodontists its constituent societies Am Board Orthodontics"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1007\/s40268-016-0153-9","article-title":"A guide to medications inducing salivary gland dysfunction, xerostomia, and subjective sialorrhea: A systematic review sponsored by the world workshop on oral medicine VI","volume":"17","author":"Andy","year":"2016","journal-title":"Drugs R D"},{"key":"B22","doi-asserted-by":"publisher","first-page":"1065","DOI":"10.3390\/biom11081065","article-title":"Neutrophil elastase and chronic lung disease","volume":"11","author":"Voynow","year":"2021","journal-title":"Biomolecules"},{"key":"B23","doi-asserted-by":"publisher","first-page":"1493684","DOI":"10.1155\/2023\/1493684","article-title":"Simvastatin reduces NETosis to attenuate severe asthma by inhibiting PAD4 expression","volume":"2023","author":"Yun-Rong","year":"2023","journal-title":"Oxid Med Cell Longev"},{"key":"B24","doi-asserted-by":"publisher","first-page":"3521","DOI":"10.3390\/cells11213521","article-title":"Neutrophil extracellular traps in asthma: friends or foes","volume":"11","author":"Remo","year":"2022","journal-title":"Cells"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2021.627328","article-title":"Interactions between neutrophils and periodontal pathogens in late-onset periodontitis","volume":"11","author":"Qingsong","year":"2021","journal-title":"Front Cell infection Microbiol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0250265","article-title":"ELISA detection of MPO-DNA complexes in human plasma is error-prone and yields limited information on neutrophil extracellular traps formed in vivo","volume":"16","author":"Hubert","year":"2021","journal-title":"PloS One"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2023.1132420","article-title":"The effect of the \u201cOral-Gut\u201d axis on periodontitis in inflammatory bowel disease: A review of microbe and immune mechanism associations","volume":"13","author":"Tianyu","year":"2023","journal-title":"Front Cell infection Microbiol"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.job.2022.09.006","article-title":"The etiological consideration of oxidized low-density lipoprotein in periodontitis","volume":"65","author":"Matsuo","year":"2022","journal-title":"J Oral Biosci"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1002\/jez.b.21259","article-title":"Odontoblasts in the dental pulp immune response","volume":"5","author":"Jean-Christophe","year":"2008","journal-title":"J Exp Zool B Mol Dev Evol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.cophys.2020.10.004","article-title":"Chemokines in cardiac fibrosis","volume":"19","author":"Ruoshui","year":"2020","journal-title":"Curr Opin Physiol"},{"key":"B31","doi-asserted-by":"publisher","first-page":"857","DOI":"10.1186\/s12903-023-03561-3","article-title":"Correlation between salivary cytokine profiles and white spot lesions in adolescent patients receiving clear aligner orthodontic treatment","volume":"23","author":"Qian","year":"2023","journal-title":"BMC Oral Health"},{"key":"B32","doi-asserted-by":"publisher","first-page":"2388","DOI":"10.3390\/ijms22052388","article-title":"Is inflammation a friend or foe for orthodontic treatment?: inflammation in orthodontically induced inflammatory root resorption and accelerating tooth movement","volume":"22","author":"Masaru","year":"2021","journal-title":"Int J Mol Sci"},{"key":"B33","doi-asserted-by":"publisher","first-page":"562","DOI":"10.3390\/antiox10040562","article-title":"The enzymatic and non-enzymatic function of myeloperoxidase (MPO) in inflammatory communication","volume":"10","author":"Yulia","year":"2021","journal-title":"Antioxidants (Basel)"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-030-44518-8_2","article-title":"Neutrophil elastase and neutrophil extracellular traps in the tumor microenvironment","volume":"1263","author":"Hai","year":"2020","journal-title":"Adv Exp Med Biol"},{"key":"B35","doi-asserted-by":"publisher","first-page":"8972","DOI":"10.1038\/s41598-017-09337-4","article-title":"CitH3: a reliable blood biomarker for diagnosis and treatment of endotoxic shock","volume":"7","author":"Baihong","year":"2017","journal-title":"Sci Rep"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1490637\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T05:26:09Z","timestamp":1746509169000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1490637\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,5,6]]},"references-count":35,"alternative-id":["10.3389\/fimmu.2025.1490637"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2025.1490637","relation":{},"ISSN":["1664-3224"],"issn-type":[{"type":"electronic","value":"1664-3224"}],"subject":[],"published":{"date-parts":[[2025,5,6]]},"article-number":"1490637"}}