ArticleAlcoholism, clinical and experimental research2013
Chronic alcohol ingestion in rats decreases Krüppel-like factor 4 expression and intracellular zinc in the lung.
Article in Alcoholism, clinical and experimental research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 22 citations in OpenAlex.
- Ethanol-induced Nrf2 suppression in the lung is mediated by AP-1-driven expression of miR-144.Alcohol, clinical & experimental research · 2025Article
- Effect of chronic alcohol exposure on gut vitamin B7 uptake: involvement of epigenetic mechanisms and effect of alcohol metabolites.American journal of physiology. Gastrointestinal and liver physiology · 2021Article
- Role of zinc insufficiency in fetal alveolar macrophage dysfunction and RSV exacerbation associated with fetal ethanol exposure.Alcohol (Fayetteville, N.Y.) · 2019Article
- Zinc deficiency as a mediator of toxic effects of alcohol abuse.European journal of nutrition · 2018Review
- The Role of Zinc and Zinc Homeostasis in Macrophage Function.Journal of immunology research · 2018Review
- Genome-wide association study of body mass index in subjects with alcohol dependence.Addiction biology · 2017Article
- Ethanol-induced changes in poly (ADP ribose) polymerase and neuronal developmental gene expression.Neuropharmacology · 2016Article
- Uptake of ascorbic acid by pancreatic acinar cells is negatively impacted by chronic alcohol exposure.American journal of physiology. Cell physiology · 2016Article
- Chronic Ethanol Exposure: Pathogenesis of Pulmonary Disease and Dysfunction.Biomolecules · 2015Review
- Molecular mechanisms of ethanol-associated oro-esophageal squamous cell carcinoma.Cancer letters · 2015Review
- Chronic alcohol exposure inhibits biotin uptake by pancreatic acinar cells: possible involvement of epigenetic mechanisms.American journal of physiology. Gastrointestinal and liver physiology · 2014Article
- Alveolar macrophage dysfunction and chronic alcohol use. Time to think about zinc.American journal of respiratory and critical care medicine · 2013Article
- Alcohol ingestion disrupts alveolar epithelial barrier function by activation of macrophage-derived transforming growth factor beta1.Respiratory research · 2013Article
- Zn metabolism of monogastric species and consequences for the definition of feeding requirements and the estimation of feed Zn bioavailability.Journal of Zhejiang University. Science. BReview
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundChronic alcohol ingestion alters the dynamic balance between granulocyte-macrophage colony-stimulating factor (GM-CSF) and transforming growth factor beta1 (TGFβ1) signaling within the alveolar space and, in parallel, impairs alveolar macrophage and epithelial cell function by inhibiting expression of the zinc importer ZIP4 and decreasing zinc bioavailability in the alveolar compartment. As the transcription factor Krüppel-like factor 4 (KLF4 ) binds to ZIP4 , we hypothesized that alcohol exposure and consequent perturbations in GM-CSF and TGFβ1 signaling could decrease cellular KLF4 expression and/or binding as a mechanism by which it inhibits ZIP4 expression and decreases cellular zinc levels. METHODS AND
resultsAlcohol exposure in vitro or chronic ingestion in vivo decreased KLF4 expression in alveolar macrophages and epithelial cells. Treatment with GM-CSF or TGFβ1 showed an enhancing or dampening effect on KLF4 expression and binding, respectively. Further, treatment of a rat alveolar macrophage cell line with alcohol in vitro for 4 weeks decreased the expression of the zinc transporters ZIP4 and ZNT1, and of the zinc storage protein metallothionein 1. In parallel, treating these macrophages with KLF4 siRNA decreased ZIP4 expression and decreased cellular zinc and phagocytic capacity to levels equivalent to those following alcohol exposure. In epithelial monolayers, transepithelial electrical resistance (TER) was significantly decreased by alcohol ingestion as compared with control diets, and it was restored by in vitro GM-CSF treatment. In contrast, in vitro TGFβ1 treatment of the epithelial monolayers from control-fed rats significantly decreased TER as compared with untreated control monolayers.
conclusionsTaken together, these results suggest that within the alveolar space, chronic alcohol exposure decreases KLF4 and ZIP4 expression and consequently decreases zinc transport into cells, which, in turn, impairs their function. Furthermore, the dynamic decrease in the relative influence of GM-CSF versus TGFβ1 could mediate the zinc deficiency and consequent cellular dysfunction that characterize the "alcoholic lung" phenotype.
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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.