ArticleInvestigative ophthalmology & visual science2011
TRPV1 activation is required for hypertonicity-stimulated inflammatory cytokine release in human corneal epithelial cells.
Article in Investigative ophthalmology & visual science, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
74 citing papers in PubMed, 153 citations in OpenAlex.
- Motugivatrep (SJP-0132) 0.3% Ophthalmic Suspension for Dry Eye Disease: A Randomized, Double-Masked, Placebo-Controlled, Multicenter, Phase 3 Trial.Clinical ophthalmology (Auckland, N.Z.) · 2026Trial
- Human Intervention Study to Assess the Effects of Supplementation with Olive Leaf Extract on Peripheral Blood Mononuclear Cell Gene Expression.International journal of molecular sciences · 2016Trial
- Pathological mechanisms of Sjögren's disease-related dry eye: from multiglandular dysfunction to ocular surface inflammation.International ophthalmology · 2026Review
- Mechanical activation of PIEZO1 drives AP-1-dependent PTGS2/PGE2 signaling and corneal inflammation.iScience · 2026Article
- Current and Developing Therapeutics for Dry Eye Disease: Targeting Ion Channels.Current issues in molecular biology · 2026Review
- Cord Blood Serum Attenuates Hyperosmolarity-Induced Inflammation and TRPV1 Upregulation in Conjunctival Epithelial Cells.International journal of molecular sciences · 2026Article
- Mesenchymal stem cell-derived extracellular vesicles for dry eye disease: principles, progress, and challenges.Extracellular vesicles and circulating nucleic acids · 2026Review
- Managing dry eye disease - a review of selected traditional Chinese medicine and some of their metabolites focusing on molecular mechanisms and signaling pathways.Frontiers in pharmacology · 2026Review
- Short-Term Changes in Persistent Ocular Discomfort After Add-On Motugivatrep in Patients with Dry Eye Disease: A Retrospective Observational Study.Clinical ophthalmology (Auckland, N.Z.) · 2026Article
- Pathological Interplay of ROS With Myofibroblasts: An Impediment to Corneal Restitution.Oxidative medicine and cellular longevity · 2026Review
- Modulation of corneal sensory processing and pain responses by dry eye and corneal wounding.Frontiers in cellular neuroscience · 2026Article
- Role of Chinese Medicine Monomers in Dry Eye Disease: Breaking the Vicious Cycle of Inflammation.Pharmacology research & perspectives · 2025Review
- Ion Channels as Potential Drug Targets in Dry Eye Disease and Their Clinical Relevance: A Review.Cells · 2024Review
- MUC1‑ND interacts with TRPV1 to promote corneal epithelial cell proliferation in diabetic dry eye mice by partly activating the AKT signaling pathway.Molecular medicine reports · 2024Article
- Review
- L-Carnitine Suppresses Transient Receptor Potential Vanilloid Type 1 Activation in Human Corneal Epithelial Cells.International journal of molecular sciences · 2023Article
- Ion channels in dry eye disease.Indian journal of ophthalmology · 2023Review
- Changes in TRPV1 Expression as Well as Substance P and Vasoactive Intestinal Peptide Levels Are Associated with Recurrence of Pterygium.International journal of molecular sciences · 2022Article
- Yanghe decoction attenuated pain hypersensitivity induced by michigan cancer foundation-7 injection in rats with bone metastases from breast cancer by inhibiting transient receptor potential ankyrin 1.Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan · 2022Article
- Article
14 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
purposeTo determine whether hypertonic stress promotes increases in inflammatory cytokine release through transient receptor potential vanilloid channel type 1 (TRPV1) signaling pathway activation in human corneal epithelial cells (HCECs).
methodsHyperosmotic medium was prepared by supplementing isotonic Ringers solution with sucrose. Ca2+ signaling was measured in fura2-AM-loaded HCECs using a single-cell fluorescence imaging system. Western blot analysis evaluated the phosphorylation status of EGFR, ERK, p38 MAPK, and nuclear factor (NF)-κB. ELISA assessed the effect of TRPV1 activation on the release of IL-6 and IL-8.
resultsA 450 mOsm hypertonic stress elicited 2-fold Ca2+ transients that were suppressed by the TRPV1-selective antagonists capsazepine and JYL 1421. Such transients were enhanced by PGE2. Hypertonicity-induced EGF receptor (EGFR) transactivation was suppressed by preincubating HCECs with capsazepine, matrix metalloproteinase 1 (MMP1) inhibitor TIMP-1, broad-spectrum MMP inhibitor GM 6001, heparin-bound (HB)-EGF inhibitor CRM 197, or EGFR inhibitor AG 1478. ERK and p38 MAPK and NF-κB activation after EGFR transactivation occurred in tonicity and in a time-dependent manner. Hypertonicity-induced increases in IL-6 and IL-8 releases were suppressed by exposure to capsazepine, AG 1478, ERK inhibitor PD 98059, p38 inhibitor SB 203580, or NF-κB inhibitor PDTC.
conclusionsHypertonic stress-elicited TRPV1 channel stimulation mediates increases in a proinflammatory cytokine IL-6 and a chemoattractant IL-8 by eliciting EGFR transactivation, MAPK, and NF-κB activation. Selective drug modulation of either TRPV1 activity or its signaling mediators may yield a novel approach to suppressing inflammatory responses occurring in dry eye syndrome.
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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.