Reference - Detail
|Author||Tanaka H, Fukuda K, Ishida W, Harada Y, Sumi T, Fukushima A.|
|Title||Rebamipide increases barrier function and attenuates TNFα-induced barrier disruption and cytokine expression in human corneal epithelial cells.|
|Journal||Br J Ophthalmol|
BACKGROUND:Disruption of corneal epithelial barrier function by inflammation may contribute to the development of dry eye. The effects of rebamipide, a drug used for the treatment of dry eye, on barrier function and cytokine expression in a human corneal epithelial (HCE) cell line were examined.
METHODS:Barrier function of HCE cells was evaluated by measurement of transepithelial electrical resistance (TER). The subcellular localisation of the tight junction protein zonula occludens (ZO)-1 was examined by immunofluorescence analysis. The release of cytokines was determined with ELISAs, and the intracellular abundance of cytokine mRNAs was quantitated by reverse transcription and real-time PCR analysis. Degradation of the nuclear factor-κB inhibitor IκBα was detected by immunoblot analysis.
RESULTS:Rebamipide increased TER of HCE cells in a concentration-dependent manner as well as attenuating the loss of TER and the disappearance of ZO-1 from the cell surface induced by tumour necrosis factor α (TNFα). Rebamipide also suppressed TNFα-induced expression of interleukin-6 and interleukin-8 at the mRNA and protein levels and inhibited the TNFα-induced degradation of IκBα.
CONCLUSIONS:The upregulation of barrier function and the anti-inflammatory effects of rebamipide, together with its mucin secretagogue activity, may contribute to the effectiveness of this drug for the treatment of dry eye.
|MeSH||Alanine / analogs & derivatives* Alanine / pharmacology Antioxidants / pharmacology* Cell Membrane Permeability / drug effects Cells, Cultured Cytokines / genetics Cytokines / metabolism* Dose-Response Relationship, Drug Electric Impedance Enzyme-Linked Immunosorbent Assay Epithelium, Corneal / drug effects* Epithelium, Corneal / metabolism Fluorescent Antibody Technique, Indirect Humans I-kappa B Proteins / metabolism Immunoblotting Quinolones / pharmacology* RNA, Messenger / metabolism Reverse Transcriptase Polymerase Chain Reaction Tight Junctions / drug effects* Tight Junctions / metabolism Tumor Necrosis Factor-alpha / antagonists & inhibitors* Tumor Necrosis Factor-alpha / pharmacology Zonula Occludens-1 Protein / metabolism|
|Human and Animal Cells||HCE-T(RCB2280)|