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Effect of Diquafosol on Hyperosmotic Stress-induced Tumor Necrosis Factor-α and Interleukin-6 Expression in Human Corneal Epithelial Cells.
- Source :
-
Korean journal of ophthalmology : KJO [Korean J Ophthalmol] 2020 Feb; Vol. 34 (1), pp. 1-10. - Publication Year :
- 2020
-
Abstract
- Purpose: Diquafosol is a pharmaceutical drug used for dry eye treatment with a novel mechanism of action. It is a purinergic P2Y2 receptor agonist that promotes the secretion of tears and healing of corneal epithelial wounds. However, its inhibitory effect on hyperosmotic stress-induced inflammation in human corneal epithelial cells (HCECs) remains unclear.<br />Methods: A hyperosmotic stress model was established by transferring HCECs from isosmotic (312 mOsm/kg to hyperosmotic medium (500 mOsm/kg). HCECs were incubated with 500 mOsm/kg hyperosmotic medium for 30 minutes, and then treated with diquafosol (0.6-6 mg/mL) for 4 or 24 hours. Cells were then harvested and analyzed by western blot, immunocytochemistry, and real-time polymerase chain reaction to evaluate the expression of interleukin-6, tumor necrosis factor-alpha, and the phosphorylation status of nuclear factor-kappa B.<br />Results: Diquafosol significantly decreased the mRNA and protein expression of hyperosmotic stress-induced tumor necrosis factor-alpha and interleukin-6. These results were supported by immunofluorescence staining and quantitative real-time polymerase chain reaction analysis. Furthermore, diquafosol inhibits nuclear factor-kappa B activation by suppressing the phosphorylation and degradation of the inhibitor of кB.<br />Conclusions: This study shows that diquafosol inhibits nuclear factor-kappa B signaling and inflammatory factors induced by hyperosmotic stress in HCECs. This suggests that using diquafosol for the improvement of dry eye syndrome could be effective in the treatment of inflammation-related corneal and conjunctival diseases.<br />Competing Interests: No potential conflict of interest relevant to this article was reported.<br /> (© 2020 The Korean Ophthalmological Society.)
- Subjects :
- Blotting, Western
Cells, Cultured
Dry Eye Syndromes genetics
Dry Eye Syndromes metabolism
Dry Eye Syndromes pathology
Epithelium, Corneal drug effects
Epithelium, Corneal pathology
Humans
Interleukin-6 biosynthesis
Ophthalmic Solutions
RNA metabolism
Signal Transduction
Tears metabolism
Tumor Necrosis Factor-alpha biosynthesis
Tumor Necrosis Factor-alpha drug effects
Tumor Necrosis Factor-alpha genetics
Epithelium, Corneal metabolism
Gene Expression Regulation drug effects
Interleukin-6 genetics
Polyphosphates pharmacology
RNA genetics
Uracil Nucleotides pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 2092-9382
- Volume :
- 34
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Korean journal of ophthalmology : KJO
- Publication Type :
- Academic Journal
- Accession number :
- 32037744
- Full Text :
- https://doi.org/10.3341/kjo.2019.0046