Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Jul 21.
doi: 10.1111/clr.70002. Online ahead of print.

Neutrophil Extracellular Traps Induce Pyroptosis of Gingival Fibroblasts in Peri-Implantitis

Jiangbo Li  1   2   3 , Zhixin Li  1   2   3 , Kailibinuer Abuduwaili  1   2   3 , Jiaying Song  1   2   3 , Yue Sun  1   2   3 , Zhuofan Chen  1   2   3 , Danying Chen  1   2   3 , Baoxin Huang  1   2   3
Affiliations

Neutrophil Extracellular Traps Induce Pyroptosis of Gingival Fibroblasts in Peri-Implantitis

Jiangbo Li et al. Clin Oral Implants Res. .

Abstract

Objectives: This study aimed to verify the release of neutrophil extracellular traps (NETs) in peri-implantitis and explore whether NETs induce pyroptosis and inflammatory responses in human gingival fibroblasts (HGFs).

Materials and methods: Peri-implant soft tissue samples were collected from healthy individuals and patients with peri-implantitis. NETs and the expression of pyroptosis-related factors including NLRP3, Caspase1, GSDMD, and IL-1β were detected. In vitro, NETs induced from differentiated HL60 (dHL60) cells and human neutrophils were used to stimulate HGFs. Transcriptome sequencing analysis and functional enrichment analysis were performed to analyze the influence of NETs on programmed cell death and inflammatory-related signaling pathways in HGFs. Further investigations were conducted to explore the changes in cell viability, cell membrane permeability, and the expression levels of inflammatory factors and pyroptosis-related markers in HGFs treated with NETs in the presence or absence of DNase I.

Results: Compared to healthy samples, the release of NETs was significantly elevated in soft tissues with peri-implantitis, accompanied by increased expression of NLRP3, Caspase1, GSDMD, and IL-1β. Functional enrichment analyses revealed that NETs activated signaling pathways related to pyroptosis and inflammatory responses of HGFs. Meanwhile, the results of the in vitro study revealed that NETs reduced cell viability, increased cell membrane permeability, and upregulated expression of inflammatory cytokines and pyroptosis markers in HGFs, which were partially reversed by DNase I treatment.

Conclusion: NETs may exacerbate the pathological progression of peri-implantitis by inducing pyroptosis and inflammatory responses in HGFs. Targeting NETs may offer a potential therapeutic strategy to mitigate the inflammation in peri-implantitis.

Keywords: gingival fibroblasts; neutrophil extracellular traps; peri‐implantitis; pyroptosis.

PubMed Disclaimer

Similar articles

See all similar articles

References

    1. Al‐Bakri, S. M. R., A. Magan‐Fernandez, P. Galindo‐Moreno, et al. 2024. “Detection and Comparison of Neutrophil Extracellular Traps in Tissue Samples of Peri‐Implantitis, Periodontitis, and Healthy Patients: A Pilot Study.” Clinical Implant Dentistry and Related Research 26: 631–641. https://doi.org/10.1111/cid.13325.
    1. Atteberry, B., B. P. Berman, T. K. Kelly, and J. Cayford. 2024. “Understanding the Complex Chromatin Dynamics in Primary Human Neutrophils During PMA‐Induced NET Formation.” Frontiers in Immunology 15: 1445638. https://doi.org/10.3389/fimmu.2024.1445638.
    1. Berglundh, T., G. Armitage, M. G. Araujo, et al. 2018. “Peri‐Implant Diseases and Conditions: Consensus Report of Workgroup 4 of the 2017 World Workshop on the Classification of Periodontal and Peri‐Implant Diseases and Conditions.” Journal of Periodontology 89, no. Suppl 1: S313–S318. https://doi.org/10.1002/jper.17‐0739.
    1. Brinkmann, V., U. Reichard, C. Goosmann, et al. 2004. “Neutrophil Extracellular Traps Kill Bacteria.” Science 303, no. 5663: 1532–1535. https://doi.org/10.1126/science.1092385.
    1. Bryzek, D., I. Ciaston, E. Dobosz, et al. 2019. “Triggering NETosis via Protease‐Activated Receptor (PAR)‐2 Signaling as a Mechanism of Hijacking Neutrophils Function for Pathogen Benefits.” PLoS Pathogens 15, no. 5: e1007773. https://doi.org/10.1371/journal.ppat.1007773.

LinkOut - more resources