Chronic obstructive pulmonary disease (COPD), a disease responsible for early mortality worldwide, is well accepted to be associated with periodontitis epidemiologically. Although both of the diseases are the multi-microbial inflammatory disease, the precise underlying mechanisms by which periodontitis influences the progression of COPD remains largely unknown. Here, we established COPD accompanied with periodontitis mouse models and observed the pronounced progress in pulmonary symptoms and histopathology, characterized by poorer respiratory function, thickened bronchial walls, and increased neutrophils infiltration in lung tissue. Mechanistically, periodontitis pathogen Porphyromonas gingivalis (P. gingivalis) relocated in the lung through the respiratory tract and LPS from P. gingivalis promoted the secretion of chemokines CXCL2 and G-CSF of alveolar epithelial cells through NF-κB and p38 MAPK pathways to recruit neutrophils. Furthermore, exposure to P. gingivalis of infiltrated neutrophils released matrix metallopeptidase-8 (MMP-8) and neutrophil elastase (NE), which aggravated airway inflammation and tissue damage. These findings indicated that periodontitis could exacerbate COPD via its pathogen P. gingivalis, which translocated in the lung and stimulated neutrophil chemotaxis and activation in the lung.
This study investigates the role of Interleukin 17 (IL-17) in exacerbating periapical lesions caused by Porphyromonas gingivalis (Pg) lipopolysaccharides (LPS) in the context of metabolic disease and its potential impact on glucose tolerance. Researchers developed a unique mouse model where mice were monocolonized with Pg to induce periapical lesions. After 1 month, they were fed a high-fat diet (HFD) for 2 months to simulate metabolic disease and oral microbiota dysbiosis. To explore the role of LPS from Pg, wild-type (WT) mice were challenged with purified LPS from Porphyromonas gingivalis, as well as with LPS-depleted and non-depleted Pg bacteria; IL-17 knockout (KO) mice were also included to assess the role of IL-17 signaling. The impact on bone lysis, periapical injury, glucose intolerance, and immune response was assessed. Results showed that in WT mice, the presence of LPS significantly worsened bone lysis, Th17 cell recruitment, and periapical injury. IL-17 KO mice exhibited reduced bone loss, glucose intolerance, and immune cell infiltration. Additionally, inflammatory markers in adipose tissue were lower in IL-17 KO mice, despite increased dysbiosis. The findings suggest that IL-17 plays a critical role in amplifying Pg-induced periapical lesions and systemic metabolic disturbances. Targeting IL-17 recruitment could offer a novel approach to improving glycemic control and reducing type 2 diabetes (T2D) risk in individuals with periapical disease.
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