ArticleThe ocular surface2021
IL-36α/IL-36RA/IL-38 signaling mediates inflammation and barrier disruption in human corneal epithelial cells under hyperosmotic stress.
Article in The ocular surface, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 28 citations in OpenAlex.
- Immunobiological Properties and Clinical Applications of Interleukin-38 for Immune-Mediated Disorders: A Systematic Review Study.International journal of molecular sciences · 2021Pooled it
- The IL-36 Cytokine Rheostat: Hierarchical Regulation of Epithelial-Immune Crosstalk and Precision Therapy in Psoriatic and Related Dermatoses.Clinical, cosmetic and investigational dermatology · 2026Review
- Anti-Inflammatory Cytokine Signatures in Primary Glaucoma Subtypes: Diagnostic and Pathophysiological Insights From IL-36Ra, IL-37, and IL-38.Journal of ophthalmology · 2026Article
- Protective Effects of miR-16-5p and miR-142-3p on Inflammation and Autophagy in Human Corneal Epithelial Cells Under Hyperosmotic Stress In Vitro.International journal of molecular sciences · 2025Article
- L-carnitine partially restores adherens junction integrity and promotes wound healing in human corneal epithelial cells exposed to hyperosmolar stress.Experimental eye research · 2025Article
- Destructive and protective effects and therapeutic targets of IL-36 family cytokines in dry eye disease.The ocular surface · 2025Article
- The Role of TRPV1/CGRP Pathway Activated byInternational journal of molecular sciences · 2025Article
- Ectoine Enhances Mucin Production Via Restoring IL-13/IFN-γ Balance in a Murine Dry Eye Model.Investigative ophthalmology & visual science · 2024Article
- Transmembrane Protein CMTM6 Alleviates Ocular Inflammatory Response and Improves Corneal Epithelial Barrier Function in Experimental Dry Eye.Investigative ophthalmology & visual science · 2024Article
- Multidimensional immunotherapy for dry eye disease: current status and future directions.Frontiers in ophthalmology · 2024Review
- 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
- Patients with hidradenitis suppurativa are associated with risk of new-onset glaucoma: a propensity-score-matched cohort study.International journal of medical sciences · 2024Article
- New insights on IL‑36 in intestinal inflammation and colorectal cancer (Review).Experimental and therapeutic medicine · 2023Review
- Evaluation of Conventional and Hyaluronic Acid-Coated Thymoquinone Liposomes in an In Vitro Model of Dry Eye.Pharmaceutics · 2023Article
- Imbalanced IL-37/TNF-α/CTSS signaling disrupts corneal epithelial barrier in a dry eye model in vitro.The ocular surface · 2022Article
- Secreted Ly-6/uPAR-related protein-1 (SLURP1) is a pro-differentiation factor that stalls G1-S transition during corneal epithelial cell cycle progression.The ocular surface · 2022Article
- Hyperosmolarity disrupts tight junctionInternational journal of ophthalmology · 2022Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
Abstract
purposeTo explore the distinct expression and diverse roles of IL-36 cytokines in dry eye disease using an in vitro hyperosmolarity model of human corneal epithelial cells (HCECs).
methodsPrimary HCECs were cultured from fresh donor limbal explants. Hyperosmolarity model was established by switching HCECs from isosmotic (312 mOsM) to hyperosmotic medium (350-500 mOsM) alone or with addition of rhIL-36RA or rhIL-38 for 2-48 h. Some cultures were treated with IL-36α (1-10 ng/ml) with or without rhIL-36RA or rhIL-38. Gene expression was detected by RT-qPCR; and protein production and barrier disruption were evaluated by ELISA and/or immunofluorescent staining.
resultsIL-36 cytokines were differential expressed in primary HCECs. Among 3 pro-inflammatory agonists, IL-36α, but not IL-36β and IL-36γ, was distinctly induced at osmolarity-dependent manner while two antagonist IL-36RA and IL-38 were significantly suppressed in HCECs exposed to hyperosmotic stress. IL-36α increased to 4.4-fold in mRNA and 6.9-fold at protein levels (116.0 ± 36.33 pg/ml vs 16.79 ± 6.51 pg/ml in controls) by 450 mOsM, but dramatically inhibited by addition of rhIL-36RA or rhIL-38. Exogenous rhIL-36α stimulated expression of TNF-α and IL-1β at mRNA and protein levels and disrupted tight junction proteins ZO-1 and occludin. However, rhIL-36RA or rhIL-38 suppressed TNF-α and IL-1β production and protected HCECs from barrier disruption in response to IL-36α or hyperosmolarity.
conclusionsOur findings demonstrate that the stimulated pro-inflammatory IL-36α with the suppressed antagonists IL-36RA and IL-38 is a novel mechanism by which hyperosmolarity induces inflammation in dry eye. IL-36RA and IL-38 may have a therapeutic potential in dry eye.
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