Pathogenesis of COPD at the cellular and molecular level

Stefano, Antonino Di; Gnemmi, Isabella; Dossena, Francesca; Ricciardolo, Fabio L. M.; Maniscalco, Mauro; Bello, Federica Lo; Balbi, Bruno

doi:10.23736/s0026-4806.22.07927-7

Cited by 12 publications

(3 citation statements)

References 160 publications

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“…COPD breaks the cross-talk among various immune cells and the balance of pro-inflammatory and anti-inflammatory responses, resulting in chronic airway inflammation, airway remodeling and tissue damage. 41 Fibroblasts increase in the lung tissue of COPD patients, and moreover, Th1/Tc1 cells, Th17 cells, activated B cells, and NK cells present within lung fibroblasts induce specific tissue damage and inflammation. Due to the downregulation or loss-of-function of TGF-β1 (transforming growth factor-beta 1), FOXP3 (forkhead box P3), CTLA-4 (cytotoxic T-lymphocyte-associated protein 4) and antioxidants in the lung tissue of COPD patients, an anti-inflammatory response is diminished.…”

Section: Discussionmentioning

confidence: 99%

Causal Involvement of Immune Cells in Chronic Obstructive Pulmonary Disease: A Mendelian Randomization Study

Guan,

Qin,

et al. 2024

COPD

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Background The immune cells play a substantial role in the development and progression of chronic obstructive pulmonary disease (COPD). We aim to investigate the causal involvement of immune cells in COPD via a Mendelian randomization (MR) analysis. Methods Published genome-wide association studies (GWAS) statistics on immune cells were analyzed, with genetic variants identified as instrumental variables (IVs). Inverse-variance weighting (IVW), weighted median, and MR-Egger regression methods were employed, along with simple mode and weighted mode adopted in the two-sample MR analysis. Sensitivity analysis was conducted to examine the heterogeneity, horizontal pleiotropy, and stability of the causal relationship. Results IVW results suggested that CCR2 on CD62L+ plasmacytoid dendritic cells (DC), CCR2 on plasmacytoid DC, CD11b on CD66b++ myeloid cells, CD19 on CD20− CD38− CD24+ memory B cell subset, CD25 on transitional B cells, and CD25++CD8br %CD8br T cells were risk factors for the development of COPD. Besides, CD127 on effector memory-like cytotoxic T lymphocytes lacking expression of co-stimulatory molecule 28 (CD28-EM CTLs) and HLA DR+ NK ACs expressing human leukocyte antigen DR molecules while being natural killer cells (%NK ACs) were protective factors for COPD. Conclusion This study unveiled a causal relationship between immune cell phenotype and COPD. These findings offer new insights for the prevention and treatment of COPD using COPD-associated immune cells.

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Section: Discussionmentioning

confidence: 99%

Causal Involvement of Immune Cells in Chronic Obstructive Pulmonary Disease: A Mendelian Randomization Study

Guan,

Qin,

et al. 2024

COPD

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“…Chronic obstructive pulmonary disease (COPD) is distinguished by gradual airway inflammation accompanied by a significant influx of inflammatory cells towards the lungs, remodeling of the airways, compromised respiratory mechanics, and decreased airflow to the alveoli [1][2][3].…”

Section: Introductionmentioning

confidence: 99%

Involvement of GPR43 Receptor in Effect of Lacticaseibacillus rhamnosus on Murine Steroid Resistant Chronic Obstructive Pulmonary Disease: Relevance to Pro-Inflammatory Mediators and Oxidative Stress in Human Macrophages

Sá,

Olímpio,

Vasconcelos

et al. 2024

Nutrients

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Background: Cytokine storm and oxidative stress are present in chronic obstructive pulmonary disease (COPD). Individuals with COPD present high levels of NF-κB-associated cytokines and pro-oxidant agents as well as low levels of Nrf2-associated antioxidants. This condition creates a steroid-resistant inflammatory microenvironment. Lacticaseibacillus rhamnosus (Lr) is a known anti-cytokine in lung diseases; however, the effect of Lr on lung inflammation and oxidative stress in steroid-resistant COPD mice remains unknown. Objective: Thus, we investigated the Lr effect on lung inflammation and oxidative stress in mice and macrophages exposed to cigarette smoke extract (CSE) and unresponsive to steroids. Methods: Mice and macrophages received dexamethasone or GLPG-094 (a GPR43 inhibitor), and only the macrophages received butyrate (but), all treatments being given before CSE. Lung inflammation was evaluated from the leukocyte population, airway remodeling, cytokines, and NF-κB. Oxidative stress disturbance was measured from ROS, 8-isoprostane, NADPH oxidase, TBARS, SOD, catalase, HO-1, and Nrf2. Results: Lr attenuated cellularity, mucus, collagen, cytokines, ROS, 8-isoprostane, NADPH oxidase, and TBARS. Otherwise, SOD, catalase, HO-1, and Nrf2 were upregulated in Lr-treated COPD mice. Anti-cytokine and antioxidant effects of butyrate also occurred in CSE-exposed macrophages. GLPG-094 rendered Lr and butyrate less effective. Conclusions: Lr attenuates lung inflammation and oxidative stress in COPD mice, suggesting the presence of a GPR43 receptor-dependent mechanism also found in macrophages.

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“…In the last years, evidence has emerged regarding autophagy activation in Chronic Obstructive Pulmonary Disease (COPD) [2,8,9], a heterogeneous lung condition characterized by chronic respiratory symptoms and persistent airflow obstruction [10]. This activation is deemed to be mainly due to cigarette smoking, as induced autophagy is considered fundamental in maintaining cellular homeostasis in adverse environments.…”

Section: Introductionmentioning

confidence: 99%

Impaired autophagy in the lower airways and lung parenchyma in stable COPD

Levra,

Rosani,

Gnemmi

et al. 2023

ERJ Open Res

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BackgroundThere is increasing evidence of autophagy activation in COPD, but its role is complex and probably regulated through cell type-specific mechanisms. This study aims to investigate the autophagic process at multiple levels within the respiratory system, using different methods to clarify conflicting results reported so far.MethodsThis cross-sectional study was performed on bronchial biopsies and peripheral lung samples obtained from COPD patients (30 and 12 per sample type, respectively) and healthy controls (25 and 22 per sample type, respectively), divided by smoking history. Subjects were matched for age and smoking history. We analysed some of the most important proteins involved in autophagosome formation, such as LC3 and p62, as well as some molecules essential for lysosome function, such as LAMP1. Immunohistochemistry was used to assess the autophagic process in both sample types. ELISA and transcriptomic analysis were performed on lung samples.ResultsWe found increased autophagic stimulus in smoking subjects, regardless of respiratory function. This was revealed by immunohistochemistry through a significant increase in LC3 (p<0.01) and LAMP1 (p<0.01) in small airway bronchiolar epithelium, alveolar septa, and alveolar macrophages. Similar results were obtained in bronchial biopsy epithelium by evaluating LC3B (p<0.05), also increased in homogenate lung tissue using ELISA (p<0.05). Patients with COPD, unlike the others, showed an increase in p62 by ELISA (p<0.05). No differences were found in transcriptomics analysis.ConclusionsDifferent techniques, applied at post-transcriptional level, confirm that cigarette smoke stimulates autophagy at multiple levels inside the respiratory system, and that autophagy failure may characterise COPD.

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Pathogenesis of COPD at the cellular and molecular level

Cited by 12 publications

References 160 publications

Causal Involvement of Immune Cells in Chronic Obstructive Pulmonary Disease: A Mendelian Randomization Study

Causal Involvement of Immune Cells in Chronic Obstructive Pulmonary Disease: A Mendelian Randomization Study

Involvement of GPR43 Receptor in Effect of Lacticaseibacillus rhamnosus on Murine Steroid Resistant Chronic Obstructive Pulmonary Disease: Relevance to Pro-Inflammatory Mediators and Oxidative Stress in Human Macrophages

Impaired autophagy in the lower airways and lung parenchyma in stable COPD

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