Department of Stomatology, Beijing Chao-Yang Hospital, Capital Medical University, 8th Gongti South Road, Beijing, 100020, China; Department of Periodontology, Tianjin Stomatological Hospital, Hospital of Stomatology, Nankai University, 75th Dagu North Road, Tianjin, 300000, China.
State Key Laboratory of Molecular Oncology, National Cancer Center/ National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, 17(th) Panjiayuan Nanli, Beijing, 100021, China.
Mol Immunol. 2020 Jan;117:110-121. doi: 10.1016/j.molimm.2019.11.003. Epub 2019 Nov 22.
Although granulocyte colony-stimulating factor(G-CSF) has pathogenic roles in several immune inflammatory diseases, its role in periodontitis has not been investigated. Here we detected local expression of G-CSF using public datasets in the Gene Expression Omnibus (GEO) database, and immune cell infiltration into gingival tissue was estimated based on single-sample gene set enrichment analysis (ssGSEA). G-CSF expression and neutrophil infiltration were also confirmed by human gingival biopsies analysis. Moreover, anti-G-CSF neutralizing antibody was locally administrated to investigate the effects of G-CSF neutralization on neutrophils infiltration and periodontal tissue destruction in periodontitis mice model. Two public datasets (GSE10334 and GSE16134), which included 424 patients with periodontitis and 133 health controls, were used in the analysis. Markedly increased immune cell infiltration and G-CSF expression in gingival tissues were found in the periodontitis group as compared to the control group. The higher expression of G-CSF was correlated with higher infiltration of immune cells, especially with neutrophil infiltration. Analysis of gingival biopsies further confirmed high neutrophil infiltration and G-CSF expression. In addition, anti-G-CSF antibody-treated mice with periodontitis showed significantly reduced alveolar bone resorption and neutrophil infiltration when compared with periodontitis mice treated with isotype control antibody. Also, anti-G-CSF antibody treatment significantly reduced mRNA expression of CXC chemokines (CXCL1, CXCL2 and CXCL3), interleukin 1β (IL-1β), IL-6, matrix metalloproteinases 9, receptor activator of nuclear factor κB ligand/osteoprotegerin (RANKL/OPG) ratio and osteoclasts number in periodontal tissues. In summary, neutrophil infiltration and G-CSF expression levels were significantly increased in inflamed gingival tissues. G-CSF neutralization in periodontal inflammation could alleviate neutrophil infiltration and periodontal tissue destruction in experimental periodontitis.
虽然粒细胞集落刺激因子 (G-CSF) 在几种免疫炎症性疾病中具有致病性作用，但它在牙周炎中的作用尚未得到研究。在这里，我们使用基因表达综合数据库 (GEO) 中的公共数据集检测 G-CSF 的局部表达，并基于单样本基因集富集分析 (ssGSEA) 估计牙龈组织中免疫细胞的浸润情况。通过对人牙龈活检的分析，还证实了 G-CSF 的表达和中性粒细胞的浸润。此外，局部给予抗 G-CSF 中和抗体，以研究 G-CSF 中和对牙周炎小鼠模型中性粒细胞浸润和牙周组织破坏的影响。我们分析了两个公共数据集（GSE10334 和 GSE16134），其中包括 424 名牙周炎患者和 133 名健康对照者。与对照组相比，牙周炎组的牙龈组织中免疫细胞浸润和 G-CSF 表达明显增加。G-CSF 的高表达与免疫细胞的高浸润相关，特别是与中性粒细胞浸润相关。牙龈活检的分析进一步证实了高中性粒细胞浸润和 G-CSF 表达。此外，与用同种型对照抗体治疗的牙周炎小鼠相比，用抗 G-CSF 抗体治疗的牙周炎小鼠的牙槽骨吸收和中性粒细胞浸润明显减少。抗 G-CSF 抗体治疗还显著降低了牙周组织中趋化因子 (CXCL1、CXCL2 和 CXCL3)、白细胞介素 1β (IL-1β)、IL-6、基质金属蛋白酶 9、核因子 κB 配体/骨保护素 (RANKL/OPG) 比值和破骨细胞数量的 mRNA 表达。总之，在炎症性牙龈组织中，中性粒细胞浸润和 G-CSF 表达水平显著增加。在牙周炎炎症中中和 G-CSF 可减轻实验性牙周炎中的中性粒细胞浸润和牙周组织破坏。
