Auraptene Mitigates Cigarette Smoke and Lipopolysaccharide‐Induced Chronic Obstructive Pulmonary Disease in Mice and BEAS‐2B Cells via Regulating Keap1/Nrf2/HO‐1 Pathway

Journal of Biochemical and Molecular Toxicology, Journal Year: 2025, Volume and Issue: 39(5)

Published: April 23, 2025

ABSTRACT Chronic obstructive pulmonary disease (COPD) is a most common respiratory condition characterized by airflow limitation, airway inflammation, and lung injury. The present study was undertaken to unveil the therapeutic potentials of auroptene against lipopolysaccharide (LPS) cigarette smoke (CS)‐induced COPD in mice. CS along with LPS exposed healthy C57BL/6 mice through intranasal route induce COPD. exposure continued for 12 weeks. challenge occurred on weeks 2, 4, 6, 8. auraptene treated orally gavage 1 h before last 4 After completion treatment, function assessed using test equipment. levels mucin proteins, extracellular matrix (ECM) proliferative cytokine markers, epithelial marker protein E‐cadherin, oxidative stress‐related biomarkers, inflammation‐associated markers were respective commercial assay kits. An analysis histopathology histo‐morphology conducted tissues. vitro assays condensate (CSC) LPS‐challenged BEAS‐2B cells. expressions Keap1/Nrf2/HO‐1 pathway associated proteins findings current work has clearly proved that at 25 mg/kg concentrations significantly increased functions treatment effectively reduced ECM levels, inflammation‐related In addition, antioxidants mitigated tissue injuries signaling successfully regulated CSC LPS‐induced Therefore, highlighted capability be beneficial intervention treat

Language: Английский

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Emerging Concepts in Cytokine Regulation of Airway Remodeling in Asthma

Immunological Reviews, Journal Year: 2025, Volume and Issue: 330(1)

Published: March 1, 2025

Asthma, a chronic respiratory condition that has seen dramatic rise in prevalence over the past few decades, now affects more than 300 million people globally and imposes significant burden on healthcare systems. The key pathological features of asthma include inflammation, airway hyperresponsiveness, mucus cell metaplasia, smooth muscle hypertrophy, subepithelial fibrosis. Cytokines released by lung epithelial cells, stromal immune cells during are critical to tissue remodeling asthma. Over researchers have made great strides understanding involved cytokines they produce. Epithelial as well many adaptive innate activated environmental signals produce cytokines, namely, type 2 (IL-4, IL-5, IL-13), IFN-γ, IL-17, TGF-β, multiple IL-6 family members. However, precise mechanisms through which these contribute remain elusive. Additionally, types can same making it challenging decipher how specific uniquely pathogenesis. This review highlights recent advances provides comprehensive overview production modulate

Language: Английский

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The role of the NLRP3 inflammasome in the pathogenesis of asthma: inflammatory mechanisms and emerging therapeutic strategies

Kazan medical journal, Journal Year: 2025, Volume and Issue: unknown

Published: March 24, 2025

This article focuses on the pathophysiological mechanisms and therapeutic potential in management of bronchial asthma, a global health challenge with increasing prevalence. The pathogenesis asthma is rooted immune-mediated inflammation involving formation inflammasomes, molecular complexes that regulate inflammatory responses. Inflammasomes, particularly NLRP3, play pivotal role disease development by interacting allergens initiating signaling cascades lead to production pro-inflammatory cytokines such as interleukin-1β (IL-1β) Interleukin-18. These recruit immune cells, including mast eosinophils, T-lymphocytes, which contribute airway inflammation, hyperreactivity, obstruction. examines phenotypes, infection-dependent atopic well association between NLRP3 inflammasome activation impaired lung function, steroid resistance, neutrophilic inflammation. Special attention given cellular involved process, interaction T-helper macrophages, leading release histamine, heparin, lysosomal enzymes, reactive oxygen species, nitric oxide, prostaglandins, leukotrienes. Inflammatory mediators IL-4, IL-5, IL-13 remodeling, mucus hypersecretion, spasm. Furthermore, can disrupt epithelial barrier exacerbating allergic study highlights chronic changes tree caused prolonged It emphasizes importance regulation, use selective inhibitor MCC950, effectively reduces demonstrates promising for asthma. concludes underscoring integrating research into clinical practice, suggesting targeted therapy, could transform treatment. need shift toward personalized medicine managing diseases like

Language: Английский

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Elevated Urotensin-II and TGF-β Levels in COPD: Biomarkers of Fibrosis and Airway Remodeling in Smokers

Medicina, Journal Year: 2024, Volume and Issue: 60(11), P. 1750 - 1750

Published: Oct. 24, 2024

Small airway fibrosis plays a critical role in the progression of chronic obstructive pulmonary disease (COPD). Previous research has suggested that Urotensin-II (U-II) and transforming growth factor-β (TGF-β) may contribute to pathological various organs, including cardiovascular system, lungs, liver. However, their specific relationship with COPD not yet been thoroughly investigated. This study aims evaluate concentrations U-II TGF-β individuals COPD, as well healthy smokers non-smokers, explore potential roles COPD-related fibrosis.

Language: Английский

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Discovering the role of microRNAs and exosomal microRNAs in chest and pulmonary diseases: a spotlight on chronic obstructive pulmonary disease

Molecular Genetics and Genomics, Journal Year: 2024, Volume and Issue: 299(1)

Published: Nov. 11, 2024

Language: Английский

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Silencing SMAD4 inhibits inflammation and ferroptosis in asthma by blocking the IL-17A signaling pathway

Respiratory Research, Journal Year: 2024, Volume and Issue: 25(1)

Published: Dec. 6, 2024

The TGF-β/SMAD signaling pathway is crucial in the pathogenesis of asthma. However, SMAD family member 4 (SMAD4), a key mediator TGF-β, its roles and underlying mechanisms asthma remain unclear. vivo vitro SMAD4 were investigated through an ovalbumin (OVA)-induced mouse model interleukin-13 (IL-13)-induced cell model. molecular mechanism influenced was examined using transcriptome sequencing, followed by feedback experiments involving recombinant human interleukin 17 A (rhIL-17 A), IL-17 activator. highly expressed models. silencing alleviated damage to lung tissue decreased inflammatory infiltration. Expression levels Caspase-3, IgG, factors reduced after SMAD4. Silencing suppressed ferroptosis. also enhanced IL-13-induced BEAS-2B proliferation apoptosis. Furthermore. promoted models, as evidenced elevated IL-17RA, A, Act1 protein levels. inhibited expression these pathway-associated proteins. Moreover, rhIL-17 treatment notably reversed impacts on OVA-induced model, indicating that inflammation ferroptosis blocking pathway. prevents inhibiting pathway, which provides novel potential approach for therapy.

Language: Английский

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Inhibition of long non-coding RNA NEAT1 suppressed the epithelial mesenchymal transition through the miR-204-5p/Six1 axis in asthma

PLoS ONE, Journal Year: 2024, Volume and Issue: 19(10), P. e0312020 - e0312020

Published: Oct. 18, 2024

Background Asthma, a prevalent chronic respiratory condition, is characterized by airway remodeling. Long non-coding RNA (lncRNA) NEAT1 has been demonstrated to participate in fibrosis. Furthermore, the miR-204-5p/Six1 axis significantly influences epithelial mesenchymal transition (EMT). However, function of NEAT1/miR-204-5p/Six1 asthmatic EMT remains unclear. Purpose This study intends elucidate EMT. Methods TGF-β1 was used induce model BEAS-2B cells. Immunofluorescence and western blot were executed verify establishment model. NEAT1, miR-204-5p, Six1 expression levels evaluated using RT-qPCR. The role vitro explored CCK8 assays flow cytometry. luciferase reporter assay performed validate interaction between miR-204-5p/Six1. Results increased during Functional experiments showed that knockdown suppressed cell proliferation promoted apoptosis . inhibition decreased N-cadherin, vimentin, α-SMA E-cadherin. Mechanistically, identified as sponge for found be direct target miR-204-5p. Conclusion Down-regulation reduced via targeting miR-204-5p inhibit process asthma. may provide new insight reveal underlying mechanisms

Language: Английский

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Epithelial-immune interactions govern type 2 immunity at barrier surfaces

Current Opinion in Immunology, Journal Year: 2024, Volume and Issue: 91, P. 102501 - 102501

Published: Nov. 10, 2024

Language: Английский

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