論文 - 詳細
| RRC ID | 44247 |
|---|---|
| 著者 | Kimura K, Morita Y, Orita T, Haruta J, Takeji Y, Sonoda KH. |
| タイトル | Protection of human corneal epithelial cells from TNF-α-induced disruption of barrier function by rebamipide. |
| ジャーナル | Invest Ophthalmol Vis Sci |
| Abstract |
PURPOSE:TNF-α disrupts the barrier function of cultured human corneal epithelial (HCE) cells. We investigated the effects of the cytoprotective drug rebamipide on this barrier disruption by TNF-α as well as on corneal epithelial damage in a rat model of dry eye. METHODS:The barrier function of HCE cells was evaluated by measurement of transepithelial electrical resistance. The distribution of tight-junction (ZO-1, occludin) and adherens-junction (E-cadherin, β-catenin) proteins, and the p65 subunit of nuclear factor-κB (NF-κB) was determined by immunofluorescence microscopy. Expression of junctional proteins as well as phosphorylation of the NF-κB inhibitor IκB-α and myosin light chain (MLC) were examined by immunoblot analysis. A rat model of dry eye was developed by surgical removal of exorbital lacrimal glands. RESULTS:Rebamipide inhibited the disruption of barrier function as well as the downregulation of ZO-1 expression, and the disappearance of ZO-1 from the interfaces of neighboring HCE cells induced by TNF-α. It also inhibited the phosphorylation and downregulation of IκB-α, the translocation of p65 to the nucleus, the formation of actin stress fibers, and the phosphorylation of MLC induced by TNF-α in HCE cells. Treatment with rebamipide eyedrops promoted the healing of corneal epithelial defects as well as attenuated the loss of ZO-1 from the surface of corneal epithelial cells in rats. CONCLUSIONS:Rebamipide protects corneal epithelial cells from the TNF-α-induced disruption of barrier function by maintaining the distribution and expression of ZO-1 as well as the organization of the actin cytoskeleton. Rebamipide is, thus, a potential drug for preventing or ameliorating the loss of corneal epithelial barrier function associated with ocular inflammation. |
| 巻・号 | 54(4) |
| ページ | 2572-760 |
| 公開日 | 2013-4-17 |
| DOI | 10.1167/iovs.12-11294 |
| PII | iovs.12-11294 |
| PMID | 23482463 |
| MeSH | Adherens Junctions / drug effects Alanine / analogs & derivatives* Alanine / pharmacology Animals Antioxidants / pharmacology* Cadherins / metabolism Cell Line Disease Models, Animal Dose-Response Relationship, Drug Dry Eye Syndromes / drug therapy Dry Eye Syndromes / metabolism Electric Impedance Epithelium, Corneal / drug effects* Epithelium, Corneal / metabolism Epithelium, Corneal / pathology Fluorescent Antibody Technique, Indirect Humans I-kappa B Proteins Immunoblotting Male NF-KappaB Inhibitor alpha NF-kappa B Occludin / metabolism Ophthalmic Solutions Phosphorylation Quinolones / pharmacology* Rats Rats, Sprague-Dawley Tight Junctions / drug effects Tumor Necrosis Factor-alpha / toxicity* Wound Healing / drug effects Zonula Occludens-1 Protein / metabolism beta Catenin / metabolism |
| IF | 4.099 |
| 引用数 | 19 |
| WOS 分野 | PHARMACOLOGY & PHARMACY TOXICOLOGY |
| リソース情報 | |
| ヒト・動物細胞 | HCE-T(RCB2280) |