CD131 antagonism blocks inflammation, emphysema and fibrosis in an asthma‐COPD overlap mouse model originating in early life

Respirology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 15, 2025

Abstract Background and Objective Asthma‐COPD overlap (ACO) is characterized by patients exhibiting features of both asthma COPD. Currently, there no specific treatment for ACO. This study aimed to investigate the therapeutic potential targeting CD131, a shared receptor subunit IL‐3, IL‐5 GM‐CSF, in ACO development preventing acute viral exacerbations. Methods A two‐hit mouse model was established house dust mite (HDM) allergen sensitization asthma, elastase emphysema. In separate model, human rhinovirus 1b (RV1b) used induce an exacerbation. neutralizing antibody against CD131 block vivo signalling. Results Mice exposed HDM developed cardinal COPD, including airway hyperreactivity (AHR) mixed granulocytic inflammatory profile identified lungs, expansion monocyte‐derived macrophages, neutrophils eosinophils. RT‐qPCR analysis detected heightened gene expression Mmp12 , Il5 Il13 . Transcriptomic further revealed pathway enrichment type 2 inflammation macrophage activation. Blockade effectively reduced lung prevented AHR, fibrosis Interestingly, Th1 response interferon production not affected treatment. Consistently, antagonism RV1b‐induced exacerbation without compromising RV1b clearance. Conclusion signalling coordinates multiple pathological pathways that drive remodelling Hence, represents novel approach combating immunopathology complex setting.

Language: Английский

The protective role of muscone in the development of COPD

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: Feb. 17, 2025

Background Muscone, a key component of musk, exhibits anti-inflammatory properties. However, its therapeutic potential in inflammatory lung diseases, such as chronic obstructive pulmonary disease (COPD), remains largely unexplored. This study aimed to investigate whether Muscone could exert protective effect mouse model COPD vivo . Methods A animal was established by exposing mice cigarette smoke (CS) and administering lipopolysaccharide (LPS) intranasally. After 4 weeks, were treated daily with dexamethasone (DEX) or different doses for 3 weeks. Mouse body weight, function, histopathology determined. Serum levels cytokines (IL-38, IL-1β, IL-17, TGF-β, IFN-γ) measured using ELISA qRT-PCR. Lung expression CXCR3, IFN-γ, IL-17A, RORγt assessed immunofluorescence. Results The weight significantly lower than that Muscone-treated mice, consistent decreased accompanied reduced circulating IL-38 levels. administration, function improved, upregulation cytokines, including IL-38, dose-dependent manner, while the pro-inflammatory reduced. Additionally, inhibited protein tissues mice. Conclusion demonstrates improves COPD, potentially through mechanism may involve modulation cytokine expression, IL-38. precise underlying mechanisms Muscone’s effects remain be fully elucidated. Further research is needed correlation between pathophysiology specific treatment, more detailed analysis balance pro- mediators models, particularly utilizing GKO further role mediating Muscone.

Language: Английский

Aerosolized nicotine-free e-liquid base constituents exacerbates mitochondrial dysfunction and endothelial glycocalyx shedding via the AKT/GSK3β-mPTP pathway in lung injury models

Respiratory Research, Journal Year: 2025, Volume and Issue: 26(1)

Published: March 1, 2025

Smoking has been recognized as a risk factor of cancer, heart disease, stroke, diabetes, and lung diseases such chronic obstructive pulmonary nicotine appears to be the responsible component tobacco smoke that affects development. While nicotine-free electronic cigarettes (e-cigarettes) are often promoted safer alternative traditional smoking, recent evidence suggests they might pose significant health risks. This study investigates effects e-cigarette vapor (ECV) on tissue endothelial function. A mouse model ECV-induced injury human microvascular cells (HPMVECs) were utilized evaluate impact ECV exposure mitochondrial function, cell viability, glycocalyx shedding. significantly damages tissue, characterized by alveolar enlargement, inflammation, vascular remodeling, indicative emphysematous changes. In vitro, HPMVECs exposed extract (ECE) demonstrated dose-dependent increases in reactive oxygen species (ROS), membrane depolarization, mPTP opening, reduced ATP production, leading enhanced permeability degradation. The inhibition opening with Cyclosporin (CsA) was found mitigate dysfunction damage induced ECE, indicating protective role preserving integrity. AKT/GSK3β signaling pathway identified key regulator these processes, ECE downregulating p-AKT p-GSK3β, thereby promoting opening. Activation AKT partially reversed effects, highlighting potential targeting AKT/GSK3β-mPTP axis adverse These findings underscore risks associated e-cigarettes suggest novel therapeutic targets for preventing progression.

Language: Английский