Objective To investigate the critical role of macrophage M1 polarization in mediating the effect of periodontitis on the progression of chronic obstructive pulmonary disease (COPD).

Methods Alveolar lavage fluid samples were collected from COPD patients with comorbid periodontitis, and gene expression analysis was performed to validate the changes in the expression of M1 polarization-related genes. A mouse model of COPD, with experimentally induced periodontitis, were established. Hematoxylin and eosin (HE) staining of pathological sections was performed to observe the effect of periodontitis on COPD progression. Flow cytometry, immunofluorescence staining, and reverse transcription quantitative polymerase chain reaction (RT-qPCR) were performed to analyze the effect of periodontitis on macrophage M1 polarization and the expression of relevant genes in the alveolar lavage fluid and lung tissues.

Results In clinical samples of alveolar lavage fluid from COPD patients with periodontitis, the expression of macrophage M1 polarization-related genes, including CD86, inducible nitric oxide synthase (iNOS), interleukin (IL)-1β, tumor necrosis factor (TNF)-α, IL-23, and IL-6, was upregulated compared with that of COPD patients without periodontitis. Analysis of a mouse disease model revealed that periodontitis affected the growth of COPD mice, with the final body mass of mice in the periodontitis and COPD comorbid group (21.3 ± 0.52 g, day 34) lower than that of the COPD group (23.93 ± 0.45 g, day 34). Pathological sections of the lung tissue showed that periodontitis exacerbated COPD progression, with more pronounced alveolar expansion and alveolar wall destruction observed in the periodontitis and COPD comorbid group. Flow cytometry revealed a higher proportion of M1-polarized macrophages in alveolar lavage fluid from COPD and periodontitis comorbid mice (31.36 ± 2.51%) compared with the COPD mice (23.19 ± 1.07%). Immunofluorescence assays indicated that periodontitis also promoted macrophage M1 polarization in the lung tissue of COPD mice. Gene expression analysis demonstrated that M1 polarization-related gene expression was significantly upregulated in both the alveolar lavage fluid and lung tissue of mice in the COPD and periodontitis co-morbid group compared to the COPD group.

Conclusion  Periodontitis exacerbates COPD progression by promoting macrophage M1 polarization in the lungs. Enhancing oral hygiene management and targeting the inhibition of macrophage M1 polarization may represent new therapeutic strategies for the clinical prevention and control of COPD.