ArticleAmerican journal of physiology. Lung cellular and molecular physiology2015
The relative balance of GM-CSF and TGF-β1 regulates lung epithelial barrier function.
Article in American journal of physiology. Lung cellular and molecular physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 56 citations in OpenAlex.
- Downregulation of RORα by alcohol promotes TGFβ and α-SMA expression in mouse lung fibroblasts.Frontiers in medicine · 2026Article
- Alcohol alters blood-testis barrier function in an in vitro model.F&S science · 2025Article
- Circular RNA RORβ regulates TGFβR1 in alcohol-induced fibroblast-to-myofibroblast differentiation.Scientific reports · 2025Article
- Development of a multi-analysis model using an epithelial-fibroblast co-culture system as an alternative to animal testing.Environmental analysis, health and toxicology · 2024Article
- Chronic alcohol use primes bronchial cells for altered inflammatory response and barrier dysfunction during SARS-CoV-2 infection.American journal of physiology. Lung cellular and molecular physiology · 2023Article
- Ethanol-exposed lung fibroblasts cause airway epithelial barrier dysfunction.Alcohol, clinical & experimental research · 2023Article
- Role of early growth response 1 in inflammation-associated lung diseases.American journal of physiology. Lung cellular and molecular physiology · 2023Review
- YES-associated protein-regulated Smad7 worsen epithelial barrier injury of chronic sinusitis with nasal polyps.Immunity, inflammation and disease · 2023Article
- Steen solution protects pulmonary microvascular endothelial cells and preserves endothelial barrier after lipopolysaccharide-induced injury.The Journal of thoracic and cardiovascular surgery · 2023Article
- Loss of GM-CSF-dependent instruction of alveolar macrophages in COVID-19 provides a rationale for inhaled GM-CSF treatment.Cell reports. Medicine · 2022Article
- Tight Junctions, the Epithelial Barrier, and Toll-like Receptor-4 During Lung Injury.Inflammation · 2022Review
- The role of human mast cells in allergy and asthma.Bioengineered · 2022Review
- The Impact of Alcohol Use Disorder on Tuberculosis: A Review of the Epidemiology and Potential Immunologic Mechanisms.Frontiers in immunology · 2022Review
- A New Immortalized Human Alveolar Epithelial Cell Model to Study Lung Injury and Toxicity on a Breathing Lung-On-Chip System.Frontiers in toxicology · 2022Article
- A hitchhiker's guide through the COVID-19 galaxy.Clinical immunology (Orlando, Fla.) · 2021Review
- Malondialdehyde-Acetaldehyde Adduct Formation Decreases Immunoglobulin A Transport across Airway Epithelium in Smokers Who Abuse Alcohol.The American journal of pathology · 2021Article
- Functional human iPSC-derived alveolar-like cells cultured in a miniaturized 96‑Transwell air-liquid interface model.Scientific reports · 2021Article
- Asymmetric distribution of dynamin-2 and β-catenin relative to tight junction spikes in alveolar epithelial cells.Tissue barriers · 2021Article
- In well-differentiated primary human bronchial epithelial cells, TGF-American journal of physiology. Lung cellular and molecular physiology · 2021Article
- TGF-β1 increases permeability of ciliated airway epithelia via redistribution of claudin 3 from tight junction into cell nuclei.Pflugers Archiv : European journal of physiology · 2021Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Lung barrier dysfunction is a cardinal feature of the acute respiratory distress syndrome (ARDS). Alcohol abuse, which increases the risk of ARDS two- to fourfold, induces transforming growth factor (TGF)-β1, which increases epithelial permeability and impairs granulocyte/macrophage colony-stimulating factor (GM-CSF)-dependent barrier integrity in experimental models. We hypothesized that the relative balance of GM-CSF and TGF-β1 signaling regulates lung epithelial barrier function. GM-CSF and TGF-β1 were tested separately and simultaneously for their effects on lung epithelial cell barrier function in vitro. TGF-β1 alone caused an ∼ 25% decrease in transepithelial resistance (TER), increased paracellular flux, and was associated with projections perpendicular to tight junctions ("spikes") containing claudin-18 that colocalized with F-actin. In contrast, GM-CSF treatment induced an ∼ 20% increase in TER, decreased paracellular flux, and showed decreased colocalization of spike-associated claudin-18 with F-actin. When simultaneously administered to lung epithelial cells, GM-CSF antagonized the effects of TGF-β1 on epithelial barrier function in cultured cells. Given this, GM-CSF and TGF-β1 levels were measured in bronchoalveolar lavage (BAL) fluid from patients with ventilator-associated pneumonia and correlated with markers for pulmonary edema and patient outcome. In patient BAL fluid, protein markers of lung barrier dysfunction, serum α2-macroglobulin, and IgM levels were increased at lower ratios of GM-CSF/TGF-β1. Critically, patients who survived had significantly higher GM-CSF/TGF-β1 ratios than nonsurviving patients. This study provides experimental and clinical evidence that the relative balance between GM-CSF and TGF-β1 signaling is a key regulator of lung epithelial barrier function. The GM-CSF/TGF-β1 ratio in BAL fluid may provide a concentration-independent biomarker that can predict patient outcomes in ARDS.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.