ArticlePloS one2014
Cortisol biosynthesis in the human ocular surface innate immune response.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 40 citations in OpenAlex.
- Parainflammation in the Ocular System: Considerations on the Underlying Mechanisms and Treatment of Dry Eye Disease.Ophthalmology and therapy · 2025Review
- Characterization of Mucosal Immune-Related lncRNAs and mRNAs in a Mouse Model of Allergic Conjunctivitis.Journal of inflammation research · 2025Article
- Dry Eye Para-Inflammation Management: Preclinical and Clinical Evidence on a Novel 0.2% Hyaluronic Acid-Based Tear Substitute with 0.001% Hydrocortisone Sodium Phosphate.Journal of clinical medicine · 2024Review
- Association Between Dry Eye Disease with Anxiety and Depression Among Medical Sciences Students in Qassim Region: Cortisol Levels in Tears as a Stress Biomarker.Journal of multidisciplinary healthcare · 2024Article
- Effectiveness of a New Active Tear Substitute Containing 0.2% Hyaluronic Acid and 0.001% Hydrocortisone on Signs and Symptoms of Dry Eye Disease by Means of Low- and High-Tech Assessments.Ophthalmology and therapy · 2024Article
- Dry Eye Para-Inflammation Treatment: Evaluation of a Novel Tear Substitute Containing Hyaluronic Acid and Low-Dose Hydrocortisone.Biomedicines · 2023Article
- Spironolactone Eyedrop Favors Restoration of Corneal Integrity after Wound Healing in the Rat.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Challenges and Opportunities in P450 Research on the Eye.Drug metabolism and disposition: the biological fate of chemicals · 2023Review
- Ocular steroidome in human eyes and in eyes with complex central serous chorioretinopathy (CSCR).Scientific reports · 2023Article
- Hormones and dry eye disease.Indian journal of ophthalmology · 2023Review
- Dealing with the Persistent Pathogenic Issues of Dry Eye Disease: The Importance of External and Internal Stimuli and Tissue Responses.Journal of clinical medicine · 2023Article
- Dry Eye Disease: What Is the Role of Vitamin D?International journal of molecular sciences · 2023Review
- Regulation of herpes simplex virus type 1 latency-reactivation cycle and ocular disease by cellular signaling pathways.Experimental eye research · 2022Article
- Evaluation of Ammonia Nitrogen Exposure in Immune Defenses Present on Spleen and Head-Kidney of Wuchang Bream (International journal of molecular sciences · 2022Article
- Modern approach to the treatment of dry eye, a complex multifactorial disease: a P.I.C.A.S.S.O. board review.The British journal of ophthalmology · 2021Review
- Native fluorescence of tear fluid as a tool for diagnostics of glaucoma.RSC advances · 2021Article
- Bilateral limbal stem cell disease in a patient with Addison's disease.BMJ case reports · 2021Article
- Signaling lipids as diagnostic biomarkers for ocular surface cicatrizing conjunctivitis.Journal of molecular medicine (Berlin, Germany) · 2020Article
- Glucocorticoid receptor signaling in the eye.Steroids · 2018Review
- Glucocorticoid action in human corneal epithelial cells establishes roles for corticosteroids in wound healing and barrier function of the eye.Experimental eye research · 2016Article
Corrections and comments
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Authors and funding
13 authors at 1 institution in 1 country.
Funding
Abstract
Innate immune responses have a critical role in regulating sight-threatening ocular surface (OcS) inflammation. While glucocorticoids (GCs) are frequently used to limit tissue damage, the role of intracrine GC (cortisol) bioavailability via 11-beta-hydroxysteroid dehydrogenase type 1 (11β-HSD1) in OcS defense, remains unresolved. We found that primary human corneal epithelial cells (PHCEC), fibroblasts (PHKF) and allogeneic macrophages (M1, GM-CSF; M2, M-CSF) were capable of generating cortisol (M1>PHKF>M2>PHCEC) but in corneal cells, this was independent of Toll-like receptor (TLR) activation. While PolyI∶C induced maximal cytokine and chemokine production from both PHCEC (IFNγ, CCL2, CCL3, and (CCL4), IL6, CXCL10, CCL5, TNFα) and PHKF (CCL2, IL-6, CXCL10, CCL5), only PHKF cytokines were inhibited by GCs. Both Poly I∶C and LPS challenged-corneal cells induced M1 chemotaxis (greatest LPS-PHKF (250%), but down-regulated M1 11β-HSD1 activity (30 and 40% respectively). These data were supported by clinical studies demonstrating reduced human tear film cortisol∶cortisone ratios (a biomarker of local 11β-HSD1 activity) in pseudomonas keratitis (1∶2.9) versus healthy controls (1∶1.3; p<0.05). This contrasted with putative TLR3-mediated OcS disease (Stevens-Johnson Syndrome, Mucous membrane pemphigoid) where an increase in cortisol∶cortisone ratio was observed (113.8∶1; p<0.05). In summary, cortisol biosynthesis in human corneal cells is independent of TLR activation and is likely to afford immunoprotection under physiological conditions. Contribution to ocular mucosal innate responses is dependent on the aetiology of immunological challenge.
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Registered trials
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