Periodontitis Aggravates Chronic Obstructive Pulmonary Disease Progression by Promoting Pulmonary Macrophage M1 Polarizations
Abstract
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.
Keywords: Chronic obstructive pulmonary disease, Periodontitis, M1 polarization, Macrophages
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PATHAK J L, YAN Y, ZHANG Q, et al. The role of oral microbiome i respiratory health and diseases. Respir Med, 2021, 185: 106475. doi: 10. 1016/j.rmed.2021.106475.
RAO W, WANG S, DULEBA M, et al. Regenerative metaplastic clones in COPD lung drive inflammation and fibrosis. Cell, 2020, 181(4): 848-864. doi: 10.1016/j.cell.2020.03.047.
ANEES UR REHMAN M, AHMAD HASSALI M A, MUHAMMAD S A, et al. The economic burden of chronic obstructive pulmonary disease (COPD) in the USA, Europe, and Asia: results from a systematic review of the literature. Expert Rev Pharmacoecon Outcomes Res, 2020, 20(6): 661-672. doi: 10.1080/14737167.2020.1678385.
RUDD K E, JOHNSON S C, AGESA K M, et al. Global, regional, and national sepsis incidence and mortality, 1990-2017: analysis for the Global Burden of Disease Study. Lancet , 2020, 395(10219): 200-211. doi: 10. 1016/S0140-6736(19)32989-7.
YANG X, ZHANG T, ZHANG Y, et al. Global burden of COPD attributable to ambient PM25 in 204 countries and territories, 1990 to 2019: a systematic analysis for the Global Burden of Disease Study 2019. Sci Total Environ, 2021, 796: 148819. doi: 10.1016/j.scitotenv.2021. 148819.
ADELOYE D, SONG P, ZHU Y, et al. Global, regional, and national prevalence of, and risk factors for, chronic obstructive pulmonary disease (COPD) in 2019: a systematic review and modelling analysis. Lancet Respir Med, 2022, 10(5): 447-458. doi: 10.1016/S2213-2600(21)00511-7.
WANG C, XU J, YANG L, et al. Prevalence and risk factors of chronic obstructive pulmonary disease in China (the China Pulmonary Health [CPH] study): a national cross-sectional study. Lancet, 2018, 391(10131): 1706-1717. doi: 10.1016/S0140-6736(18)30841-9.
SALVI S S, BARNES P J. Chronic obstructive pulmonary disease in non-smokers. Lancet , 2009, 374(9691): 733-743. doi: 10.1016/S0140-6736(09) 61303-9.
WANG J M, WANG C, LI G. Progress in research of chronic obstructive pulmonary disease and risk factors. Chin J Epidemiol, 2022, 43(8): 1343-1348. doi: 10.3760/cma.j.cn112338-20211228-01022.
LIETZAN A D, SIMPSON J B, WALTON W G, et al. Microbial β-glucuronidases drive human periodontal disease etiology. Sci Adv, 2023, 9(18): eadg3390. doi: 10.1126/sciadv.adg3390.
MOLINA A, HUCK O, HERRERA D, et al. The association between respiratory diseases and periodontitis: a systematic review and meta-analysis. J Clin Periodontol, 2023, 50(6): 842-887. doi: 10.1111/jcpe.13767.
QIAN Y, YUAN W, MEI N, et al. Periodontitis increases the risk of respiratory disease mortality in older patients. Exp Gerontol, 2020, 133: 110878. doi: 10.1016/j.exger.2020.110878.
TAKEUCHI K, MATSUMOTO K, FURUTA M, et al. Periodontitis is associated with chronic obstructive pulmonary disease. J Dent Res, 2019, 98(5): 534-540. doi: 10.1177/0022034519833630.
LIU J, OUYANG Y, ZHANG Z, et al. The role of Th17 cells: explanation of relationship between periodontitis and COPD? Inflamm Res, 2022, 71(9): 1011-1024. doi: 10.1007/s00011-022-01602-1.
ZHOU X, WANG J, LIU W, et al. Periodontal status and microbiologic pathogens in patients with chronic obstructive pulmonary disease and periodontitis: a case-control study. Int J Chron Obstruct Pulmon Dis, 2020, 15: 2071-2079. doi: 10.2147/COPD.S266612.
LEE J W, CHUN W, LEE H J, et al. The role of macrophages in the development of acute and chronic inflammatory lung diseases. Cells, 2021, 10(4): 897. doi: 10.3390/cells10040897.
SUN X, LIU Y, FENG X, et al. The key role of macrophage depolarization in the treatment of COPD with ergosterol both in vitro and in vivo. Int Immunopharmacol, 2020, 79: 106086. doi: 10.1016/j.intimp.2019.106086.
KIM G D, LIM E Y, SHIN H S. Macrophage polarization and functions in pathogenesis of chronic obstructive pulmonary disease. Int J Mol Sci, 2024, 25(11): 5631. doi: 10.3390/ijms25115631.
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