Dataset Information

New Insights into the Role of NLRP3 Inflammasome in Pathogenesis and Treatment of Chronic Obstructive Pulmonary Disease.

ABSTRACT: Chronic obstructive pulmonary disease (COPD) is an inflammatory lung disease characterized by chronic airway obstruction and emphysema. Accumulating studies have shown that the onset and development of COPD are related to an aberrant immune response induced by the dysregulation of a number of genetic and environmental factors, while the exact pathogenesis of this disease is not well defined. Emerging studies based on tests on samples from COPD patients, animal models, pharmacological and genetic data suggest that the NLR family pyrin domain containing 3 (NLRP3) inflammasome activation is required in the lung inflammatory responses in the development of COPD. Although the available clinical studies targeting the inflammasome effector cytokine, IL-1β, or IL-1 signaling do not show positive outcomes for COPD treatment, many alternative strategies have been proposed by recent emerging studies. Here, we highlight the recent progress in our understanding of the role of the NLRP3 inflammasome in COPD and propose possible future studies that may further elucidate the roles of the inflammasome in the pathogenesis or the intervention of this inflammatory lung disease.

SUBMITTER: Zhang J

PROVIDER: S-EPMC8405160 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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New Insights into the Role of NLRP3 Inflammasome in Pathogenesis and Treatment of Chronic Obstructive Pulmonary Disease.

Zhang Jie J Xu Qiuyun Q Sun Weichen W Zhou Xiaorong X Fu Da D Mao Liming L

Journal of inflammation research 20210826

Chronic obstructive pulmonary disease (COPD) is an inflammatory lung disease characterized by chronic airway obstruction and emphysema. Accumulating studies have shown that the onset and development of COPD are related to an aberrant immune response induced by the dysregulation of a number of genetic and environmental factors, while the exact pathogenesis of this disease is not well defined. Emerging studies based on tests on samples from COPD patients, animal models, pharmacological and genetic ...[more]

PMID: 34471373

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Project description:BackgroundAirway remodeling and inflammation are considered the main characteristics of chronic obstructive pulmonary disease (COPD). Cigarette smoke promotes the occurrence of inflammation, oxidative stress, and pyroptosis. Halotherapy has been shown to dilute secretions in the airways and promote drainage, but the mechanism remains unclear. In this study, we evaluated the anti-inflammatory and antioxidant effects of halotherapy in COPD rats and investigated the underlying mechanism.MethodsA COPD rat model was constructed by cigarette smoke and lipopolysaccharide tracheal instillation. A total of 120 male Sprague-Dawley (SD) rats were randomly divided into control, model, halotherapy, terbutaline, halotherapy + terbutaline, and Ac-YVAD-CMK (Caspase-1 inhibitor) groups. After modeling and treatment, the pulmonary function of the rats was measured. Pathological changes in the lungs were measured by hematoxylin-eosin (H&E) staining. Serum interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), interleukin-4 (IL-4), and nitric oxide (NO) levels were determined using enzyme-linked immunosorbent assay (ELISA) kits. Malondialdehyde (MDA) levels and superoxide dismutase (SOD) activity in the lungs were determined by biochemical tests. The levels of cluster of differentiation 4 (CD4+) and CD8+ T cells in the blood were determined by flow cytometry. The expression levels of Toll-like receptor 4 (TLR4), nuclear factor kappa B (NF-κB), gasdermin-D (GSDMD), nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3), apoptosis-associated speck-like protein containing a C-terminal caspase recruitment domain (ASC), Caspase-1, and IL-1β in lung tissues were detected by immunohistochemistry, Western blotting, or quantitative polymerase chain reaction (qPCR).ResultsHalotherapy recovered the clinical symptoms of COPD rats, and reduced lung inflammatory cell infiltration and air wall attenuation. It also relieved oxidative stress in the lung tissue of COPD rats, reduced CD4+ and CD8+ T cell accumulation in lung tissue, and decreased inflammatory factor production in the serum of COPD rats. Furthermore, it inhibited the TLR4/NF-κB/GSDMD and NLRP3/ASC/Caspase-1 signaling pathways. Ac-YVAD-CMK could not completely inhibit the therapeutic effect of halotherapy on COPD rats.ConclusionsHalotherapy improves lung function by inhibiting the NLRP3/ASC/Caspase-1 signaling pathway to reduce inflammation and pyroptosis in COPD rats, and may be a new option for the prevention and treatment of COPD.

Dataset Information

New Insights into the Role of NLRP3 Inflammasome in Pathogenesis and Treatment of Chronic Obstructive Pulmonary Disease.

Publications

New Insights into the Role of NLRP3 Inflammasome in Pathogenesis and Treatment of Chronic Obstructive Pulmonary Disease.

Similar Datasets

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