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
. 2024 Sep;51(9):1210-1221.
doi: 10.1111/jcpe.14025. Epub 2024 Jun 5.

Elevated neutrophil extracellular trap levels in periodontitis: Implications for keratinization and barrier function in gingival epithelium

Ya-Yun Cui  1 , Yi-Heng Yang  2 , Jia-Yi Zheng  2 , Hui-Hui Ma  2 , Xue Han  1 , Chong-Shan Liao  1 , Min Zhou  1
Affiliations

Elevated neutrophil extracellular trap levels in periodontitis: Implications for keratinization and barrier function in gingival epithelium

Ya-Yun Cui et al. J Clin Periodontol. 2024 Sep.

Abstract

Aim: To explore the levels of neutrophil extracellular traps (NETs) in patients with periodontitis and examine their effects on keratinization, barrier function of human gingival keratinocytes (HGKs) and the associated mechanisms.

Materials and methods: Saliva, gingival crevicular fluid (GCF), clinical periodontal parameters and gingival specimens were collected from 10 healthy control subjects and 10 patients with stage II-IV periodontitis to measure the NET levels. Subsequently, mRNA and protein levels of keratinization and barrier indicators, as well as intracellular calcium and epithelial barrier permeability, were analysed in HGKs after NET stimulation.

Results: The study showed that NET levels significantly elevated in patients with periodontitis, across multiple specimens including saliva, GCF and gingival tissues. Stimulation of HGKs with NETs resulted in a decrease in the expressions of involucrin, cytokeratin 10, zonula occludens 1 and E-cadherin, along with decreased intracellular calcium levels and increased epithelial barrier permeability. Furthermore, the inhibition of keratinization by NETs is ERK-KLF4-dependent.

Conclusions: This study indicates that NETs impair the barrier function of HGKs and suppress keratinization through ERK/KLF4 axis. These findings provide potential targets for therapeutic approaches in periodontitis to address impaired gingival keratinization.

Keywords: epithelial barrier; human gingival keratinocytes; keratinization; neutrophil extracellular traps; periodontitis.

PubMed Disclaimer

References

REFERENCES

    1. Arun, R., Hemalatha, R., Arun, K. V., & Kumar, T. (2010). E‐cadherin and CD1a expression in gingival epithelium in periodontal health, disease and post‐treatment. Indian Journal of Dental Research, 21, 396–401. https://doi.org/10.4103/0970-9290.70811
    1. Ben Lagha, A., Yang, Y., Trivedi, H. M., Masters, J. G., & Grenier, D. (2021). A dual zinc plus arginine formulation protects against tumor necrosis factor‐alpha‐induced barrier dysfunction and enhances cell proliferation and migration in an in vitro gingival keratinocyte model. Archives of Oral Biology, 126, 105126. https://doi.org/10.1016/j.archoralbio.2021.105126
    1. Brinkmann, V., Reichard, U., Goosmann, C., Fauler, B., Uhlemann, Y., Weiss, D. S., Weinrauch, Y., & Zychlinsky, A. (2004). Neutrophil extracellular traps kill bacteria. Science, 303, 1532–1535. https://doi.org/10.1126/science.1092385
    1. Brock, G. R., Butterworth, C. J., Matthews, J. B., & Chapple, I. L. (2004). Local and systemic total antioxidant capacity in periodontitis and health. Journal of Clinical Periodontology, 31, 515–521. https://doi.org/10.1111/j.1600-051X.2004.00509.x
    1. Bugueno, I. M., Batool, F., Keller, L., Kuchler‐Bopp, S., Benkirane‐Jessel, N., & Huck, O. (2018). Porphyromonas gingivalis bypasses epithelial barrier and modulates fibroblastic inflammatory response in an in vitro 3D spheroid model. Scientific Reports, 8, 14914. https://doi.org/10.1038/s41598-018-33267-4

Publication types

MeSH terms

LinkOut - more resources