Protection of human corneal epithelial cells from TNF-α- induced disruption of barrier function by rebamipide

Kazuhiro Kimura, Yukiko Morita, Tomoko Orita, Junpei Haruta, Yasuhiro Takeji, Koh Hei Sonoda

研究成果: ジャーナルへの寄稿学術誌査読

62 被引用数 (Scopus)

抄録

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 IκBα, 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.

本文言語英語
ページ(範囲)2752-2760
ページ数9
ジャーナルInvestigative Ophthalmology and Visual Science
54
4
DOI
出版ステータス出版済み - 2013
外部発表はい

!!!All Science Journal Classification (ASJC) codes

  • 眼科学
  • 感覚系
  • 細胞および分子神経科学

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