ArticleThe ocular surface2022
Imbalanced IL-37/TNF-α/CTSS signaling disrupts corneal epithelial barrier in a dry eye model in vitro.
Article in The ocular surface, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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The trial behind it
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Who cites it
15 citing papers in PubMed, 22 citations in OpenAlex.
- Evaluation of the therapeutic effect of estrogen replacement therapy combined with autologous serum therapy in controlling severe dry eye disease in perimenopausal women.Scientific reports · 2025Trial
- The Exercise-CTSS-AD Axis: a novel framework for understanding exercise-induced neuroprotection in Alzheimer's disease.Metabolic brain disease · 2026Review
- Piezo1 Activation by Shear Stress Induces Corneal Epithelial Homeostasis Disruption.Investigative ophthalmology & visual science · 2026Article
- Pathological mechanisms of Sjögren's disease-related dry eye: from multiglandular dysfunction to ocular surface inflammation.International ophthalmology · 2026Review
- Molecular Target Discovery and Systemic Mechanism Analysis of Teriflunomide for Dry Eye Disease.Current issues in molecular biology · 2026Article
- Molecular landscape connecting complications of dry eye disease: mechanisms, therapeutic targets, biomarkers, and future innovations.International ophthalmology · 2026Review
- Cathepsin S contributes to influenza-induced lung injury by driving inflammation, promoting apoptosis, and disrupting epithelial barrier integrity.Microbiology spectrum · 2026Article
- Wogonoside alleviates hyperosmotic stress-induced inflammation and apoptosis in human corneal epithelial cells via PI3K/AKT signaling.Frontiers in medicine · 2026Article
- Assessing the Independent and Combined Effects of Hyperosmolarity and Inflammatory Stress on Human Corneal Epithelial Cells.Investigative ophthalmology & visual science · 2025Article
- Fatty Acid Desaturase 1 Knockdown Promotes Wound Healing and Functional Recovery of the Corneal Epithelium in Diabetes.Investigative ophthalmology & visual science · 2025Article
- Destructive and protective effects and therapeutic targets of IL-36 family cytokines in dry eye disease.The ocular surface · 2025Article
- Reticulated Retinoic Acid Synthesis is Implicated in the Pathogenesis of Dry Eye in Aqp5 Deficiency Mice.Investigative ophthalmology & visual science · 2024Article
- Semaphorin 7A impairs barrier function in cultured human corneal epithelial cells in a manner dependent on nuclear factor-kappa B.International journal of ophthalmology · 2024Article
- Molecular nature of ocular surface barrier function, diseases that affect it, and its relevance for ocular drug delivery.The ocular surface · 2023Review
- Recent Advances in Hydrogels for the Diagnosis and Treatment of Dry Eye Disease.Gels (Basel, Switzerland) · 2022Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
purposeTo explore novel role and molecular mechanism of a natural anti-inflammatory cytokine interleukin (IL) 37 in preventing corneal epithelial barrier disruption from hyperosmolar stress as can occur in dry eye disease.
methodsPrimary human corneal epithelial cells (HCECs) were cultured from fresh donor limbal explants. An in vitro dry eye model with hyperosmolar stress was established by switching HCECs from isosmolar (312mOsM) to hyperosmolar medium (350-500 mOsM), and some cells were treated with rhIL-37 or rhTNF-α, for different periods (2-48 h). The expression of cytokines and cathepsin S, and barrier protein integrity were evaluated by RT-qPCR, ELISA, and immunofluorescent staining with confocal microscopy.
resultsThe integrity of epithelial barrier was significantly disrupted in HCECs exposed to hyperosmolar medium, as shown by immunofluorescent images of tight junction (TJ, ZO-1, occludin and claudin-1) and adheren junction (E-cadherin) proteins. TNF-α accentuated hyperosmolar-induced disruption of TJ barrier functional integrity whereas exposure to IL-37 blunted or even reversed these changes. Cathepsin S, encoded by CTSS gene, was found to directly disrupt epithelial barrier integrity. Interestingly, CTSS expression was significantly induced by TNF-α and hyperosmolarity, while exogenous rhIL-37 inhibited TNF-α and CTSS expression at mRNA and protein levels following hyperosmolar stress. Furthermore, rhIL-37 restored barrier protein integrity, observed in 2D and 3D confocal immunofluorescent images, in HCECs under hyperosmolar stress.
conclusionOur findings demonstrate a novel signaling pathway by which anti-inflammatory cytokine IL-37 prevents corneal epithelial barrier disruption under hyperosmotic stress via suppressing TNF-α and CTSS expression. This study provides new insight into mechanisms protecting corneal barrier in dry eye disease.
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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 Socratic graph.