Neutrophil elastase aggravates periodontitis by disrupting gingival epithelial barrier via cleaving cell adhesion molecules

Neutrophil elastase (NE) functions as a host defense factor; however, excessive NE activity can potentially destroy human tissues. Although NE activity is positively correlated to gingival crevicular fluid and clinical attachment loss in periodontitis, the underlying mechanisms by which NE aggravate...

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Published in:Scientific reports 2022-05, Vol.12 (1), p.8159-8159, Article 8159
Main Authors: Hiyoshi, Takumi, Domon, Hisanori, Maekawa, Tomoki, Tamura, Hikaru, Isono, Toshihito, Hirayama, Satoru, Sasagawa, Karin, Takizawa, Fumio, Tabeta, Koichi, Terao, Yutaka
Format: Article
Language:English
Subjects:
631/250/127
631/250/256
631/80/79
692/699/255/1318
692/699/3020/3029
Adhesion
Animal models
Bone loss
Cell adhesion & migration
Cell adhesion molecules
Cytokines
Desmoglein 1
Dextran
E-cadherin
Elastase
Fluorescein
Gingiva
Gum disease
Humanities and Social Sciences
Inflammation
Isothiocyanate
Leukocytes (neutrophilic)
multidisciplinary
Neutrophils
Periodontitis
Permeability
Science
Science (multidisciplinary)
Tissues
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Summary:Neutrophil elastase (NE) functions as a host defense factor; however, excessive NE activity can potentially destroy human tissues. Although NE activity is positively correlated to gingival crevicular fluid and clinical attachment loss in periodontitis, the underlying mechanisms by which NE aggravates periodontitis remain elusive. In this study, we investigated how NE induces periodontitis severity and whether NE inhibitors were efficacious in periodontitis treatment. In a ligature-induced murine model of periodontitis, neutrophil recruitment, NE activity, and periodontal bone loss were increased in the periodontal tissue. Local administration of an NE inhibitor significantly decreased NE activity in periodontal tissue and attenuated periodontal bone loss. Furthermore, the transcription of proinflammatory cytokines in the gingiva, which was significantly upregulated in the model of periodontitis, was significantly downregulated by NE inhibitor injection. An in vitro study demonstrated that NE cleaved cell adhesion molecules, such as desmoglein 1, occludin, and E-cadherin, and induced exfoliation of the epithelial keratinous layer in three-dimensional human oral epithelial tissue models. The permeability of fluorescein-5-isothiocyanate-dextran or periodontal pathogen was significantly increased by NE treatment in the human gingival epithelial monolayer. These findings suggest that NE induces the disruption of the gingival epithelial barrier and bacterial invasion in periodontal tissues, aggravating periodontitis.
ISSN:2045-2322
2045-2322
DOI:10.1038/s41598-022-12358-3