Department of Oral and Maxillofacial Surgery II, Nihon University School of Dentistry, Tokyo, Japan.
Department of Microbiology, Nihon University School of Dentistry, Tokyo, Japan.
In Vivo. 2022 Mar-Apr;36(2):649-656. doi: 10.21873/invivo.12749.
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.
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.
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.
F. nucleatum may contribute to the onset of pulmonary diseases via MMP9 expression through extracellular-regulated kinase 1/2 and NF-κB activation.
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。
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。
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。
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。