IL-13 facilitates ferroptotic death in asthmatic epithelial cells via SOCS1-mediated ubiquitinated degradation of SLC7A11

Redox Biology, Journal Year: 2024, Volume and Issue: 71, P. 103100 - 103100

Published: March 8, 2024

Th2-high asthma is characterized by elevated levels of type 2 cytokines, such as interleukin 13 (IL-13), and its prevalence has been increasing worldwide. Ferroptosis, a recently discovered programmed cell death, involved in the pathological process asthma; however, underlying mechanisms remain incompletely understood. In this study, we demonstrated that serum level malondialdehyde (MDA), an index lipid peroxidation, positively correlated with IL-13 negatively predicted forced expiratory volume 1 s (FEV1%) asthmatics. Furthermore, showed facilitates ferroptosis upregulating suppressor cytokine signaling (SOCS1) through analyzing immortalized airway epithelial cells, human organoids, ovalbumin (OVA)-challenged model. We identified signal transducer activator transcription 6 (STAT6) promotes SOCS1 upon stimulation. Moreover, SOCS1, E3 ubiquitin ligase, was found to bind solute carrier family 7 member 11 (SLC7A11) catalyze ubiquitinated degradation, thereby promoting cells. Last, inhibiting can decrease cells alleviate hyperresponsiveness (AHR) OVA-challenged wide-type mice, while overexpression exacerbated above IL-13-knockout mice. Our findings reveal IL-13/STAT6/SOCS1/SLC7A11 pathway novel molecular mechanism for asthma, confirming targeting potential therapeutic strategy asthma.

Language: Английский

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β-glucan mitigates ovalbumin-induced airway inflammation by preventing oxidative stress and CD8+ T cell infiltration

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 132, P. 111985 - 111985

Published: April 10, 2024

Language: Английский

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β-glucan nanoparticles alleviate acute asthma by suppressing ferroptosis and DNA damage in mice

APOPTOSIS, Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 21, 2024

Abstract Asthma is a severe respiratory disease marked by airway inflammation, remodeling, and oxidative stress. β-Glucan (BG), polysaccharide constituent of fungal cellular structures, exhibits potent immunomodulatory activities. The investigational focus was on the anti-asthmatic anti-ferroptotic properties beta-glucan nanoparticles (BG-NPs) in murine model allergic asthma induced ovalbumin (OVA). BG extracted from Chaga mushrooms ( Inonotus obliquus ), its BG-NPs were characterized utilizing techniques including FT-IR, UV visible spectroscopy, zeta potential analysis, DLS, XRD, TEM. Balb/C mice allocated into five groups: control, untreated asthmatic, dexamethasone (Dexa)-treated (1 mg/kg), BG-treated (100 BG-NPs-treated (45 mg/kg). Treatment with markedly diminished entry inflammatory cells passage, serum IgE concentrations, DNA damage, markers stress through reduction malonaldehyde (MDA) levels enhancing reduced glutathione (GSH), peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT). Furthermore, iron deposition promoted transcriptional activity GPx4 gene pulmonary cells, attenuating ferroptosis. results demonstrated that inhibiting stress, Our suggest could be used as treatments for asthma. Graphical abstract

Language: Английский

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Epithelial and immune transcriptomic characteristics and possible regulatory mechanisms in asthma exacerbation: insights from integrated studies

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

Published: Jan. 23, 2025

Background Asthma exacerbation significantly contribute to disease mortality and result in heightened health care expenditures. This study was aimed at gaining important new insights into the heterogeneity of epithelial immune cells elucidating key regulatory genes involved pathogenesis asthma exacerbation. Methods Functional enrichment, pseudotime, metabolism cell-cell communication analyses single-cell RNA sequencing (scRNA-seq) dataset were applied. Immune infiltration analysis performed bulk (bulk RNA-seq) dataset. Key obtained by taking intersection differentially expressed (DEGs) between control group cells, RNA-seq data. animal vitro cell line models established verify expression employing quantitative reverse transcription polymerase chain reaction (qRT-PCR). Results ScRNA-seq identified 7 subpopulations 14 distinct types based on gene profiles. Further demonstrated that these manifested high levels functional variations, dynamics, patterns metabolic changes. Notably, TMPRSS11A, TUBA1A, SCEL, ICAM4, TMPRSS11B, IGFBP2, CLC, NFAM1 F13A1 as asthma. The results qRT-PCR 9 Conclusions We systematically explored characteristics underlying occurrence progression, which may be valuable for providing cellular molecular mechanisms driving exacerbations.

Language: Английский

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Investigating ferroptosis-related genes NFE2L2 in neutrophils for ankylosing spondylitis: therapeutic potential of cassia twigs

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: March 10, 2025

We determined the relationship between ferroptosis and immune cells in ankylosing spondylitis role of Chinese herbal medicine Cassia twigs treating spondylitis. analyzed clinical data on spondylitis, transcriptome data, single-cell sequencing genes related to twigs. Clinical variables AS were selected through logistic regression analysis combined with machine learning. GSEA enrichment performed ferroptosis, drug-related genes, identify key drug targets AS, as well as, cells. Then, cell subtypes analyzed. Finally, interconnections intercellular communication. Five variables, including neutrophils, screened for analysis. The AUC experimental group was 0.859 that validation 0.807. Ferroptosis gene NFE2L2 identified final target AS; it upregulated downregulated control by immunohistochemical verification, both which statistically significant (P < 0.001). Neutrophils divided into two subgroups: high expression low NFE2L2. Through molecular docking, found effectively act important AS. herb can treat acting protein structure

Language: Английский

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Wuwei Shaji powder alleviates OVA-induced allergic asthma by protecting bronchial epithelial cells from ferroptosis via the S-sulfhydration of Keap1

Journal of Ethnopharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 119649 - 119649

Published: April 1, 2025

Language: Английский

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Exploring Ferroptosis in Allergic Inflammatory Diseases: Emerging Mechanisms and Therapeutic Perspectives

Cell Biology International, Journal Year: 2025, Volume and Issue: unknown

Published: April 22, 2025

ABSTRACT Ferroptosis, a unique form of regulated cell death driven by iron accumulation and lipid peroxidation, has emerged as critical process in various diseases. Recent evidence suggests its involvement the pathogenesis allergic diseases, including asthma, rhinitis, atopic dermatitis. These conditions are characterized chronic inflammation, oxidative stress, immune dysregulation, all which intersect with molecular mechanisms ferroptosis. Key regulators, such glutathione peroxidase 4 (GPX4), cystine/glutamate antiporter system Xc‐, metabolism pathways, play pivotal roles ferroptotic processes their contribution to disease progression. This review explores mechanistic link between ferroptosis emphasizing how damage overload exacerbate inflammation tissue injury. We also highlight emerging diagnostic biomarkers, peroxidation products could improve monitoring stratification. Therapeutic strategies targeting ferroptosis, GPX4 activators, chelators, inhibitors, show promise preclinical\ studies, offering potential new avenues for treating However, challenges remain translating these findings into clinical applications. By integrating current knowledge, this underscores need further research both biomarker therapeutic target

Language: Английский

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GAMG alleviates liver fibrosis through inducing ferroptosis in inflammatory macrophages via the IRF1/SLC7A11 signaling pathway

Redox Biology, Journal Year: 2025, Volume and Issue: unknown, P. 103509 - 103509

Published: Jan. 1, 2025

The activation of inflammatory macrophages plays a pivotal role in the development liver fibrosis (LF). Ferroptosis contributes to clearance and release profibrotic factors. Glycyrrhetic Acid 3-O-Mono-β-d-glucuronide (GAMG) is natural compound, potential which on LF remains uncertain. In this study, GAMG treatment significantly reduced hepatocyte steatosis, fibroplasia, cell infiltration, collagen fiber deposition mice. addition, remarkably decreased content protein improved function indicators. Single-cell RNA sequencing revealed that affected changes macrophage subsets LF, Funrich analysis identified IRF1 as key transcription factor regulating genome. was increased while ferroptosis related SLC7A11 down-regulated treated macrophages. Mass spectrometry metabolomics showed metabolites associated with LF. vivo vitro experiments further verified induced through IRF1/SLC7A11 axis, ultimately alleviated Therefore, induces by activating provides new strategy for

Language: Английский

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The Effects and Mechanisms of the YY1/EGFR Axis on Inflammation and Oxidative Stress in Asthma

Cell Biochemistry and Biophysics, Journal Year: 2025, Volume and Issue: unknown

Published: April 4, 2025

Language: Английский

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Identification of hub genes for the diagnosis associated with heart failure using multiple cell death patterns

ESC Heart Failure, Journal Year: 2025, Volume and Issue: unknown

Published: April 10, 2025

Abstract Aims Heart failure (HF) is an important public health problem worldwide, and programmed cell death (PCD) plays a crucial role in its pathologic process. This study aims to identify the hub genes associated with HF through PCD order better understand pathogenesis of improve diagnosis treatment. Methods results The gene expression dataset was obtained from GEO database. Bioinformatics machine learning algorithms were utilized screen key PCD‐related genes, diagnostic model constructed on this. Functional enrichment analysis clarified ontology signalling pathways HF. immune infiltration performed explore levels cells each gene. Through bioinformatics analysis, 95 obtained. showed that they mainly involved inflammation, immunomodulation other mechanisms. DHRS11 LRKK2 identified as PCD‐associated by algorithms. confirmed significant biomarkers training validation datasets, their nomogram had effective value. Immune imbalance T‐cell populations, monocytes macrophages M2 Conclusions In this study, genes. construction analyses performed, which provided new ideas for molecular mechanisms development

Language: Английский

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