Macrophage Polarization and Functions in Pathogenesis of Chronic Obstructive Pulmonary Disease

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(11), С. 5631 - 5631

Опубликована: Май 22, 2024

Chronic obstructive pulmonary disease (COPD), the major leading cause of mortality worldwide, is a progressive and irreversible respiratory condition characterized by peripheral airway lung parenchymal inflammation, accompanied fibrosis, emphysema, airflow limitation, has multiple etiologies, including genetic variance, air pollution, repetitive exposure to harmful substances. However, precise mechanisms underlying pathogenesis COPD have not been identified. Recent multiomics-based evidence suggests that plasticity alveolar macrophages contributes onset progression through coordinated modulation numerous transcription factors. Therefore, this review focuses on understanding functions macrophage polarization regulate homeostasis in COPD. These findings may provide better insight into distinct role perspective for developing novel therapeutic strategies targeting polarization.

Язык: Английский

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The Multi-Target Action Mechanism for the Anti-Periodontitis Effect of Astragali radix Based on Bioinformatics Analysis and In Vitro Verification

Nutrients, Год журнала: 2025, Номер 17(4), С. 627 - 627

Опубликована: Фев. 10, 2025

Background:Astragali radix is a traditional Chinese medicine with potential therapeutic effects on periodontitis; however, its underlying mechanisms require further investigation. Methods: We employed network pharmacology, molecular docking, dynamics simulations, and in vitro experiments to explore the actions of Astragali treating periodontitis. Results: A total 17 compounds (including most prevalent one, Kaempferol) from 464 corresponding targets were identified, which five major active ingredients selected based drug-active ingredient periodontitis gene network. Protein-protein interaction (PPI) analysis identified top ten core targets, seven possess suitable crystal structures for docking. These include interleukin-6 (IL6), tumor necrosis factor (TNF), AKT serine/threonine kinase 1 (AKT1), interleukin-1β (IL1β), prostaglandin G/H synthase-2 (PTGS2), matrix metalloproteinase-9 (MMP9), caspase-3 (CASP3). Additionally, 58 Gene Ontology (GO) terms 146 Kyoto Encyclopedia Genes Genomes (KEGG) pathways identified. The mentioned above subjected docking using Discovery Studio 2019 software. Molecular dynamic simulations confirmed stable between CASP3 Kaempferol ligand system. In indicated that significantly inhibited lipopolysaccharide (LPS)-induced apoptosis human periodontal ligament stem cells reduced expression levels IL6, MMP9. Conclusions: This study systematically elucidates primary derived exert their pharmacological anti-inflammation anti-apoptosis) primarily by interacting multiple targets. findings establish promising foundation targeted application treatment

Язык: Английский

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Overexpression of USP8 inhibits inflammation and ferroptosis in chronic obstructive pulmonary disease by regulating the OTUB1/SLC7A11 signaling pathway

Allergologia et Immunopathologia, Год журнала: 2024, Номер 52(4), С. 60 - 67

Опубликована: Июль 1, 2024

Background: Chronic obstructive pulmonary disease (COPD) is a familiar disease, and owns high morbidity mortality, which critically damages the health of patients. Ubiquitin-specific peptidase 8 (USP8) pivotal protein to join in regulation some diseases. In previous report, it was determined that USP8 expression down-regulated LPS-treated BEAS-2B cells, restrains inflammatory response accelerates cell viability. However, regulatory roles on ferroptosis COPD are rarely reported, associated molecular mechanisms keep vague. Objective: To investigate functions progression. Material Methods: The lung were measured through Buxco Fine Pointe Series Whole Body Plethysmography (WBP). Fe level tested assay kit. expressions assessed western blot. levels tumor necrosis -factor-α, interleukin 6, evaluated enzyme-linked immunosorbent serologic assay. Cell viability CCK-8 Results: this work, discovered overexpression improved function mice. addition, repressed by regulating glutathione peroxidase 4 acyl-CoA synthetase long-chain family Overexpression suppressed inflammation Furthermore, model. At last, verified accelerated ubiquitin aldehyde-binding 1 (OTUB1)/solute carrier 7 member 11 (SLC7A11) pathway. Conclusion: This study manifested restrained OTUB1/SLC7A11 signaling discovery hinted could be potential target for treatment.

Язык: Английский

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Targeting Immunoproteasome in Polarized Macrophages Ameliorates Experimental Emphysema Via Activating NRF1/2‐P62 Axis and Suppressing IRF4 Transcription

Advanced Science, Год журнала: 2024, Номер 11(44)

Опубликована: Окт. 2, 2024

Abstract Chronic obstructive pulmonary disease (COPD) stands as the prevailing chronic airway ailment, characterized by bronchitis and emphysema. Current medications fall short in treatment of these diseases, underscoring urgent need for effective therapy. Prior research indicated immunoproteasome inhibition alleviated various inflammatory diseases modulating immune cell functions. However, its therapeutic potential COPD remains largely unexplored. Here, an elevated expression subunits LMP2 LMP7 macrophages isolated from mouse with LPS/Elastase‐induced emphysema polarized vitro is observed. Subsequently, intranasal administration immunoproteasome‐specific inhibitor ONX‐0914 significantly mitigated COPD‐associated inflammation improved lung function mice suppressing macrophage polarization. Additionally, capsulated PLGA nanoparticles exhibited more pronounced effect on than naked targeting macrophages. Mechanistically, activated autophagy endoplasmic reticulum (ER) stress are not attribute to mediated suppression Intriguingly, inhibited M1 polarization through nuclear factor erythroid 2‐related factor‐1 (NRF1) NRF2‐P62 axis, while M2 regulated inhibiting transcription interferon regulatory 4 (IRF4). In summary, findings suggest that holds promise a strategy COPD.

Язык: Английский

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Exploration of the potential causative genes for inflammatory bowel disease: Transcriptome-wide association analysis, Mendelian randomization analysis and Bayesian colocalisation

Heliyon, Год журнала: 2024, Номер 10(7), С. e28944 - e28944

Опубликована: Апрель 1, 2024

Inflammatory bowel disease (IBD) poses a complex challenge due to its intricate underlying mechanisms, and curative treatments remain elusive. Consequently, there is an urgent need identify genes causally associated with IBD.

Язык: Английский

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Down-regulation of RTEL1 Improves M1/M2 Macrophage Polarization by Promoting SFRP2 in Fibroblasts-derived Exosomes to Alleviate COPD

Cell Biochemistry and Biophysics, Год журнала: 2024, Номер 82(3), С. 2129 - 2139

Опубликована: Май 28, 2024

Язык: Английский

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