title: Rebamipide increases barrier function and attenuates TNFα-induced barrier disruption and cytokine expression in human corneal epithelial cells.
abstract: 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.
authors.affiliation: Machida Hospital, Kochi City, Kochi, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tanaka
authors.forename: Ken
authors.initials: K
authors.lastname: Fukuda
authors.forename: Waka
authors.initials: W
authors.lastname: Ishida
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Harada
authors.forename: Tamaki
authors.initials: T
authors.lastname: Sumi
authors.forename: Atsuki
authors.initials: A
authors.lastname: Fukushima
mesh_terms: D000409:Alanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology*; D002463:Cell Membrane Permeability / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D017097:Electric Impedance; D004797:Enzyme-Linked Immunosorbent Assay; D019573:Epithelium, Corneal / Q000187:drug effects* / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D015151:Immunoblotting; D015363:Quinolones / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019108:Tight Junctions / Q000187:drug effects* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D062826:Zonula Occludens-1 Protein / Q000378:metabolism
chemical_list: D000975:Antioxidants; D016207:Cytokines; D020672:I-kappa B Proteins; D015363:Quinolones; D012333:RNA, Messenger; C569042:TJP1 protein, human; D014409:Tumor Necrosis Factor-alpha; D062826:Zonula Occludens-1 Protein; C052785:rebamipide; D000409:Alanine
keywords: Drugs; Experimental &#8211 laboratory; Inflammation; Ocular surface; Tears