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Updated: Oct 1, 2025
Robust Ligature-Induced Model of Murine Periodontitis for the Evaluation of Oral Neutrophils
Published on: January 21, 2020
Periodontopathic Bacterium Fusobacterium nucleatum Affects Matrix Metalloproteinase-9 Expression in Human Alveolar
Ryuta Suzuki1,2, Noriaki Kamio3, Kozue Sugimoto2
1Department of Oral and Maxillofacial Surgery II, Nihon University School of Dentistry, Tokyo, Japan.
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.
Insights
Fusobacterium nucleatum increases matrix metalloproteinase-9 (MMP9) in lung cells, potentially contributing to pulmonary diseases through specific signaling pathways.
Area of Science:
- Microbiology
- Pulmonology
- Molecular Biology
Background:
- Pulmonary diseases are linked to periodontopathic bacteria, but molecular mechanisms are unclear.
- Matrix metalloproteinase-9 (MMP9) is implicated in pneumonia, COPD, and asthma.
Purpose of the Study:
- To investigate the effect of Fusobacterium nucleatum on MMP9 expression.
- To elucidate the molecular pathways involved in F. nucleatum-induced MMP9 expression in lung tissues and cells.
Main Methods:
- Administered heat-killed F. nucleatum to mouse trachea and A549 human alveolar epithelial cells.
- Quantified MMP9 expression using real-time PCR and western blotting.
- Examined the roles of mitogen-activated protein kinases (MAPKs) and nuclear factor-κB (NF-κB).
Main Results:
- F. nucleatum significantly induced MMP9 expression in mouse lungs and bronchoalveolar lavage fluid.
- In A549 cells, F. nucleatum upregulated MMP9 mRNA and protein in a density-dependent manner.
- MMP9 induction was mediated by extracellular-regulated kinase 1/2 (ERK1/2) and NF-κB, but not p38 or JNK pathways.
Conclusions:
- F. nucleatum may promote pulmonary diseases by inducing MMP9 expression.
- ERK1/2 and NF-κB signaling pathways are critical in F. nucleatum-mediated MMP9 upregulation.
- This study provides insights into the molecular link between oral bacteria and lung pathology.
