Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Jan 21;25(1):31.
doi: 10.1186/s12890-024-03435-6.

NLRP3 is a BMI-independent mediator of stable COPD

Yonca Gungor  1   2 , Selin Ercan  3 , Saliha Selin Özuygur Ermiş  3 , Yiğit Kozalı  2   4 , Gizem Kursunluoglu  5 , Ceyda Sahan  6 , Aylin Ozgen Alpaydin  7 , Hulya Ayar Kayali  8   9   10
Affiliations

NLRP3 is a BMI-independent mediator of stable COPD

Yonca Gungor et al. BMC Pulm Med. .

Abstract

Purpose: The inflammatory response in animal models of chronic obstructive pulmonary disease (COPD) is activated by the NLR-family-pyrin-domain-containing-3 (NLRP3) inflammasome pathway, which is also known to play a role in obesity-related inflammation. The NLRP3/caspase-1/interleukin (IL)-1β pathway might be involved in the progression of COPD with increasing body mass index. To our knowledge, no previous studies have explored the role of NLRP3 inflammasome markers in linking COPD and obesity. Here, we aim to investigate this potential connection by examining levels of NLRP3, caspase-1, IL-1β, and IL-17A and to provide additional data on the expression of these molecules in relation to smoking status and COPD severity.

Methods: A case‒control study was conducted between July 2020 and March 2023. Peripheral blood mononuclear cells were isolated, and total RNA was extracted for real-time quantitative polymerase chain reaction (qPCR) analysis to measure the expression levels of inflammasome molecules.

Results: 29 subjects who were diagnosed with stable COPD and 32 controls were included in the data analysis. NLRP3 and IL-17A but not caspase-1 or IL-1β expression was significantly greater in the COPD group than in the control group. We detected a significant increase in NLRP3 levels in the smoker COPD group (p = 0.009) and nonsmoker COPD group (p = 0.045) compared with those in the nonsmoker control group. There was no significant correlation between BMI and the inflammasome markers.

Conclusion: As proinflammatory biomarkers, NLRP3 and IL-17A are prominent in stable COPD patients. Smoking may trigger NLRP3-mediated inflammation in stable COPD patients. The expression levels of NLRP3 inflammasome molecules did not differ in terms of disease severity or BMI.

Keywords: COPD; IL-17A; Inflammasome; NLRP3; Obesity; Smoking.

PubMed Disclaimer

Conflict of interest statement

Declarations. Ethical approval: The study was approved by the local ethics committee of Dokuz Eylul University (No: 2020/01–23, date: 6 January 2020). Consent to participate: Verbal and written informed consent to participate in this study was obtained from all individual participants. Consent to publish: Not Applicable: this manuscript does not include identifying images or other personal or clinical details of participants that compromise anonymity. Competing interests: The authors declare no competing interests. Strengths and limitations: To our knowledge, this study is among the first to investigate the impact of obesity on the NLRP3 pathway in COPD. Additionally, owing to the close proximity of our research center, blood samples were analyzed shortly after collection, ensuring data accuracy. However, our study has several limitations. This study was conducted at a tertiary care center with a small sample size, which may not accurately represent the broader COPD population. Moreover, our sample group consisted solely of stable COPD patients, which could limit the assessment of the relationship between obesity and COPD. We also acknowledge age and sex distribution limitations within the sample, which may affect the generalizability of our findings. As no exacerbations were observed for at least one month prior, potential variations in inflammasome expression linked to exacerbation periods may not have been detected. Future studies should investigate these effects during exacerbation phases and aim for a larger, multi-center cohort with balanced age and sex distribution for a more comprehensive understanding of the NLRP3 pathway’s role.

Figures

Fig. 1
Fig. 1
RQ scores of caspase-1, IL-1β, IL-17A, and NLRP3 between the COPD and control groups. The Mann‒Whitney U test was used to analyze the data. p values ≤ 0.05 were considered statistically significant. (N.S.: not significant, *p ≤ 0.05)
Fig. 2
Fig. 2
RQ scores of NLRP3 inflammasome markers based on GOLD classification. The Mann‒Whitney U test was used to analyze the data. p-values ≤ 0.05 were considered statistically significant (**p ≤ 0.01). Non-significant values are not indicated in the graph. (Sample sizes: control (n=32), GOLD A (n=5), GOLD B (n=12), GOLD E (n=12))
See this image and copyright information in PMC

References

    1. Agustí A, Celli BR, Criner GJ et al. (2023) Global initiative for chronic obstructive lung disease report: GOLD executive summary. Eur Respir J. 2023;61(4):2300239. 10.1183/13993003.00239-2023 - PMC - PubMed
    1. World Health Organization. Chronic obstructive pulmonary disease (COPD): Fact sheet. Published 2023. https://www.who.int/news-room/fact-sheets/detail/chronic-obstructive-pul.... Accessed 15 Nov 2024.
    1. Guo P, Li R, Piao TH, Wang CL, Wu XL, Cai HY. Pathological mechanism and targeted drugs of COPD. Int J Chron Obstruct Pulmon Dis. 2022;17:1565–75. 10.2147/COPD.S366126. - PMC - PubMed
    1. Donovan C, Liu G, Shen S, et al. The role of the microbiome and the NLRP3 inflammasome in the gut and lung. J Leukoc Biol. 2020;108(3):925–35. 10.1002/JLB.3MR0720-472RR. - PubMed
    1. Butler A, Walton GM, Sapey E. Neutrophilic inflammation in the Pathogenesis of Chronic Obstructive Pulmonary Disease. COPD. 2018;15(4):392–404. 10.1080/15412555.2018.1476475. - PubMed

MeSH terms

LinkOut - more resources