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牙周致病菌影响人肺泡上皮细胞和小鼠肺组织中基质金属蛋白酶-9 的表达

Periodontopathic Bacterium Affects Matrix Metalloproteinase-9 Expression in Human Alveolar Epithelial Cells and Mouse Lung.

机构信息

Department of Oral and Maxillofacial Surgery II, Nihon University School of Dentistry, Tokyo, Japan.

Department of Microbiology, Nihon University School of Dentistry, Tokyo, Japan.

出版信息

In Vivo. 2022 Mar-Apr;36(2):649-656. doi: 10.21873/invivo.12749.

Abstract

BACKGROUND/AIM: Despite evidence of an association between pulmonary diseases and periodontopathic bacteria, the molecular mechanisms remain unknown. Matrix metalloproteinase-9 (MMP9) plays important roles in pneumonia, chronic obstructive pulmonary disease, and asthma; therefore, we assessed the effects of Fusobacterium nucleatum on MMP9 expression in mouse lung and A549 human alveolar epithelial cells.

MATERIALS AND METHODS

Heat-killed F. nucleatum was administered to the trachea of mice or added to A549 cell cultures. MMP9 expression was determined using real-time PCR and western blotting. The involvement of mitogen-activated protein kinases (MAPKs) and nuclear factor-κB (NF-κB) in MMP9 expression was examined.

RESULTS

F. nucleatum induced expression of MMP9 in mouse lung and bronchoalveolar lavage fluid. In A549 cells, F. nucleatum induced production of MMP9 protein and mRNA in a density-dependent manner; this was inhibited by inhibitors of extracellular-regulated kinase 1/2 and NF-κB, but not of p38 and Jun N-terminal protein kinase.

CONCLUSION

F. nucleatum may contribute to the onset of pulmonary diseases via MMP9 expression through extracellular-regulated kinase 1/2 and NF-κB activation.

摘要

背景/目的:尽管有肺部疾病与牙周病细菌之间存在关联的证据,但分子机制尚不清楚。基质金属蛋白酶 9(MMP9)在肺炎、慢性阻塞性肺疾病和哮喘中发挥重要作用;因此,我们评估了核梭杆菌对小鼠肺和 A549 人肺泡上皮细胞中 MMP9 表达的影响。

材料与方法

热灭活的核梭杆菌通过气管内给药或添加到 A549 细胞培养物中。使用实时 PCR 和蛋白质印迹法确定 MMP9 的表达。检查丝裂原活化蛋白激酶(MAPKs)和核因子-κB(NF-κB)在 MMP9 表达中的参与。

结果

核梭杆菌诱导了小鼠肺部和支气管肺泡灌洗液中 MMP9 的表达。在 A549 细胞中,核梭杆菌以密度依赖性方式诱导 MMP9 蛋白和 mRNA 的产生;该作用可被细胞外调节激酶 1/2 和 NF-κB 的抑制剂抑制,但不能被 p38 和 Jun N-末端蛋白激酶的抑制剂抑制。

结论

核梭杆菌可能通过细胞外调节激酶 1/2 和 NF-κB 的激活,通过 MMP9 的表达促进肺部疾病的发生。

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