ArticleThe Journal of clinical investigation2022
15LO1 dictates glutathione redox changes in asthmatic airway epithelium to worsen type 2 inflammation.
Article in The Journal of clinical investigation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
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Who cites it
67 citing papers in PubMed, 121 citations in OpenAlex.
- Intranasal Curcumin and N-Acetyl l-Cysteine (NAC) Attenuates Dibutyl Phthalate (DBP)-Aggravated Airway Inflammation by Targeting Ferroptosis via Nrf-2/GPx4-SLC7A11.Environmental toxicology · 2026Article
- Fueling the fire: metabolic dysfunction and senescence as drivers of lung aging and disease.Physiological reviews · 2026Review
- 15-LOX-catalytic bias towards ether-(alkenyl)-ETE-PEs oxidation bestows selectivity of PRO-ferroptotic cell death signaling.Nature communications · 2026Article
- Exploring Biomarkers and Regulatory Mechanisms Associated with Lytic Cell Death in Allergic Rhinitis Based on Transcriptome Analysis.Biomedicines · 2026Article
- S100P mediates IL-13/ATF4-driven epithelial barrier dysfunction in eosinophilic asthma: a potential biomarker and therapeutic target.Journal of translational medicine · 2026Article
- Luteolin Attenuates Asthma Via Inhibiting ALOX15 Mediated Bronchial Epithelial Cell Ferroptosis.Inflammation · 2026Article
- Review
- Identification and Validation of ALOX15 as a Robust Diagnostic Biomarker for Obesity-Associated Asthma: An Integrative Bioinformatic and Experimental Study.Journal of inflammation research · 2026Article
- Ferroptosis as an Emerging Therapeutic Target in Allergic Diseases.Drug design, development and therapy · 2026Review
- The role of ALOX15 in inflammation-related diseases.Frontiers in immunology · 2026Review
- Stimulator of Interferon Genes Regulates Ferroptosis and Airway Inflammation via acyl-CoA Synthetase Long-Chain Family Member 4 in Asthmatic Mice.Inflammation · 2025Article
- Multi-Omics Reveals Aberrant Phenotypes of Respiratory Microbiome and Phospholipidomics Associated with Asthma-Related Inflammation.Microorganisms · 2025Article
- Investigation of key ferroptosis-associated genes and potential therapeutic drugs for asthma based on machine learning and regression models.Scientific reports · 2025Article
- MTOR signaling regulates the development of airway mucous cell metaplasia associated with severe asthma.JCI insight · 2025Article
- Multicohort Analysis of Bronchial Epithelial Cell Expression in Healthy Subjects and Patients with Asthma Reveals Four Clinically Distinct Clusters.American journal of respiratory cell and molecular biology · 2025Article
- Integrated hepatic ferroptosis gene signature dictates pathogenic features of ferroptosis.Hepatology communications · 2025Article
- Expression and clinical significance of the p53/SAT1/ALOX15 ferroptosis-associated proteins in sinonasal inverted papilloma.World journal of otorhinolaryngology - head and neck surgery · 2025Article
- Asthma Phenotypes and Biomarkers.Respiratory care · 2025Review
- Redox Imbalance in Cystic Fibrosis: The Multifaceted Role of Oxidative Stress.Pharmaceuticals (Basel, Switzerland) · 2025Review
- PEBP1 and 15-LO-1 in Asthma: Biomarker Potential for Diagnosis and Severity Stratification.Diagnostics (Basel, Switzerland) · 2025Article
7 more citing papers are in PubMed but not listed here.
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Authors and funding
16 authors at 2 institutions in 2 countries.
Funding
Abstract
Altered redox biology challenges all cells, with compensatory responses often determining a cell's fate. When 15 lipoxygenase 1 (15LO1), a lipid-peroxidizing enzyme abundant in asthmatic human airway epithelial cells (HAECs), binds phosphatidylethanolamine-binding protein 1 (PEBP1), hydroperoxy-phospholipids, which drive ferroptotic cell death, are generated. Peroxidases, including glutathione peroxidase 4 (GPX4), metabolize hydroperoxy-phospholipids to hydroxy derivatives to prevent ferroptotic death, but consume reduced glutathione (GSH). The cystine transporter SLC7A11 critically restores/maintains intracellular GSH. We hypothesized that high 15LO1, PEBP1, and GPX4 activity drives abnormal asthmatic redox biology, evidenced by lower bronchoalveolar lavage (BAL) fluid and intraepithelial cell GSH:oxidized GSH (GSSG) ratios, to enhance type 2 (T2) inflammatory responses. GSH, GSSG (enzymatic assays), 15LO1, GPX4, SLC7A11, and T2 biomarkers (Western blot and RNA-Seq) were measured in asthmatic and healthy control (HC) cells and fluids, with siRNA knockdown as appropriate. GSSG was higher and GSH:GSSG lower in asthmatic compared with HC BAL fluid, while intracellular GSH was lower in asthma. In vitro, a T2 cytokine (IL-13) induced 15LO1 generation of hydroperoxy-phospholipids, which lowered intracellular GSH and increased extracellular GSSG. Lowering GSH further by inhibiting SLC7A11 enhanced T2 inflammatory protein expression and ferroptosis. Ex vivo, redox imbalances corresponded to 15LO1 and SLC7A11 expression, T2 biomarkers, and worsened clinical outcomes. Thus, 15LO1 pathway-induced redox biology perturbations worsen T2 inflammation and asthma control, supporting 15LO1 as a therapeutic target.
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Registered trials
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