ArticleBiological research2021
Increased susceptibility of cystic fibrosis airway epithelial cells to ferroptosis.
Article in Biological research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 29 citations in OpenAlex.
- The single-cell transcriptional landscape of the pediatric cystic fibrosis lung from minimally invasive respiratory specimens.Scientific reports · 2026Article
- DNA methylation predicts lung function and pulmonary exacerbation in sputum samples from patients with cystic fibrosis.Clinical epigenetics · 2025Article
- Emerging dual role of ferroptosis in lung cancer (Review).Oncology reports · 2025Review
- Ferroptosis: molecular mechanisms, pathophysiology, and role in pediatric pulmonary diseases.Cell biology and toxicology · 2025Review
- Dietary Iron Intake Impacts the Microbial Composition of the Murine Intestinal and Lung Microbiome.Nutrients · 2025Article
- A chronicInfection and immunity · 2025Article
- Redox Imbalance in Cystic Fibrosis: The Multifaceted Role of Oxidative Stress.Pharmaceuticals (Basel, Switzerland) · 2025Review
- H3K14la drives endothelial dysfunction in sepsis-induced ARDS by promoting SLC40A1/transferrin-mediated ferroptosis.MedComm · 2025Article
- Mapping the oxidative landscape in cystic fibrosis: methodological frontiers and application.Frontiers in pharmacology · 2025Review
- The molecular and metabolic landscape of ferroptosis in respiratory diseases: Pharmacological aspects.Journal of pharmaceutical analysis · 2025Review
- Unveiling the Pathological Landscape of Intrauterine Adhesion: Mechanistic Insights and Exosome-Biomaterial Therapeutic Innovations.International journal of nanomedicine · 2025Review
- Targeting ferroptosis by natural products in pathophysiological conditions.Archives of toxicology · 2024Review
- Acute lung injury: a view from the perspective of necroptosis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2024Review
- Discovery of dysregulated circular RNAs in whole blood transcriptomes from cystic fibrosis patients - implication of a role for cellular senescence in cystic fibrosis.Journal of cystic fibrosis : official journal of the European Cystic Fibrosis Society · 2023Article
- Biofilm-forming strains of P. aeruginosa and S. aureus isolated from cystic fibrosis patients differently affect inflammatory phenotype of macrophages.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023Article
- A compensatory RNase E variation increases Iron Piracy and Virulence in multidrug-resistant Pseudomonas aeruginosa during Macrophage infection.PLoS pathogens · 2023Article
- Organelle-Specific Mechanisms in Crosstalk between Apoptosis and Ferroptosis.Oxidative medicine and cellular longevity · 2023Review
- Ferroptosis: a double-edged sword mediating immune tolerance of cancer.Cell death & disease · 2022Review
- Heme Oxygenase-1: An Anti-Inflammatory Effector in Cardiovascular, Lung, and Related Metabolic Disorders.Antioxidants (Basel, Switzerland) · 2022Review
- Physiological Effects of Ferroptosis on Organ Fibrosis.Oxidative medicine and cellular longevity · 2022Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDefective chloride transport in airway epithelial cells (AECs) and the associated lung disease are the main causes of morbidity and early mortality in cystic fibrosis (CF). Abnormal airway iron homeostasis and the presence of lipid peroxidation products, indicative of oxidative stress, are features of CF lung disease.
resultsHere, we report that CF AECs (IB3-1) are susceptible to ferroptosis, a type of cell death associated with iron accumulation and lipid peroxidation. Compared to isogenic CFTR corrected cells (C38), the IB3-1 cells showed increased susceptibility to cell death upon exposure to iron in the form of ferric ammonium citrate (FAC) and the ferroptosis inducer, erastin. This phenotype was accompanied by accumulation of intracellular ferrous iron and lipid peroxides and the extracellular release of malondialdehyde, all indicative of redox stress, and increased levels of lactate dehydrogenase in the culture supernatant, indicating enhanced cell injury. The ferric iron chelator deferoxamine (DFO) and the lipophilic antioxidant ferrostatin-1 inhibited FAC and erastin induced ferroptosis in IB3-1 cells. Glutathione peroxidase 4 (GPX4) expression was decreased in IB3-1 cells treated with FAC and erastin, but was unchanged in C38 AECs. Necroptosis appeared to be involved in the enhanced susceptibility of IB3-1 AECs to ferroptosis, as evidenced by partial cell death rescue with necroptosis inhibitors and enhanced mixed lineage kinase domain-like (MLKL) localisation to the plasma membrane.
conclusionThese studies suggest that the increased susceptibility of CF AECs to ferroptosis is linked to abnormal intracellular ferrous iron accumulation and reduced antioxidant defences. In addition, the process of ferroptotic cell death in CF AECs does not appear to be a single entity and for the first time we describe necroptosis as a potential contributory factor. Iron chelation and antioxidant treatments may be promising therapeutic interventions in cystic fibrosis.
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