中性粒细胞弹性蛋白酶上调胎盘生长因子促进牙周病的发病机制和进展。

The neutrophil elastase-upregulated placenta growth factor promotes the pathogenesis and progression of periodontal disease.

机构信息

Department of Mechanical Engineering, National Taiwan University of Science and Technology, Taipei, Taiwan.

Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei, Taiwan.

出版信息

J Periodontol. 2022 Sep;93(9):1401-1410. doi: 10.1002/JPER.21-0587. Epub 2022 Jan 25.

DOI:10.1002/JPER.21-0587

PMID:34967007

Abstract

BACKGROUND

Periodontal disease is a chronic inflammatory disease. Given its high prevalence, especially in aging population, the detailed mechanisms about pathogenesis of periodontal disease are important issues for study. Neutrophil firstly infiltrates to periodontal disease-associated pathogen loci and amplifies the inflammatory response for host defense. However, excessive neutrophil-secreted neutrophil elastase (NE) damages the affected gingival. In lung and esophageal epithelium, NE had been proved to upregulate several growth factors including placenta growth factor (PGF). PGF is an angiogenic factor with proinflammatory properties, which mediates the progression of inflammatory disease. Therefore, we hypothesize excessive NE upregulates PGF and participates in the pathogenesis and progression of periodontal disease.

METHODS

In gingival epithelial cells (GEC), growth factors array demonstrated NE-increased growth factors and further be corroborated by Western blot assay and ELISA. The GEC inflammation was evaluated by ELISA. In mice, the immunohistochemistry results demonstrated ligature implantation-induced neutrophil infiltration and growth factor upregulation. By multiplex assay, the ligature-induced proinflammatory cytokines level in gingival crevicular fluid (GCF) were evaluated. Finally, alveolar bone absorption was analyzed by micro-CT images and H & E staining.

RESULTS

NE upregulated PGF expression and secretion in GEC. PGF promoted GEC to secret IL-1β, IL-6, and TNF-α in GCF In periodontal disease animal model, ligature implantation triggered NE infiltration and PGF expression. Blockade of PGF attenuated the ligature implantation-induced IL-1β, IL-6, TNF-α and MIP-2 secretion and ameliorated the alveolar bone loss in mice.

CONCLUSION

In conclusion, the NE-induced PGF triggers gingival epithelium inflammation and promotes the pathogenesis and progression of periodontal disease.

摘要

背景

牙周病是一种慢性炎症性疾病。鉴于其高发病率，尤其是在老龄化人群中，牙周病发病机制的详细机制是重要的研究问题。中性粒细胞首先浸润到与牙周病相关的病原体部位，并放大炎症反应以进行宿主防御。然而，过多的中性粒细胞分泌的中性粒细胞弹性蛋白酶（NE）会损害受影响的牙龈。在肺和食管上皮细胞中，已经证明 NE 上调了几种生长因子，包括胎盘生长因子（PGF）。PGF 是一种具有促炎特性的血管生成因子，介导炎症性疾病的进展。因此，我们假设过量的 NE 上调 PGF 并参与牙周病的发病机制和进展。

方法

在牙龈上皮细胞（GEC）中，生长因子阵列显示 NE 增加了生长因子，进一步通过 Western blot 分析和 ELISA 验证。通过 ELISA 评估 GEC 炎症。在小鼠中，免疫组织化学结果表明结扎植入诱导中性粒细胞浸润和生长因子上调。通过多重分析，评估龈沟液（GCF）中结扎诱导的促炎细胞因子水平。最后，通过 micro-CT 图像和 H&E 染色分析牙槽骨吸收。

结果

NE 在上皮细胞中上调 PGF 的表达和分泌。PGF 促进 GEC 在 GCF 中分泌 IL-1β、IL-6 和 TNF-α。在牙周病动物模型中，结扎植入触发了 NE 浸润和 PGF 表达。PGF 阻断减轻了结扎植入诱导的 IL-1β、IL-6、TNF-α 和 MIP-2 分泌，并改善了小鼠的牙槽骨丢失。