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Kazuhiro Kimura, Shinichiro Teranishi, Ken Fukuda, Koji Kawamoto, Teruo Nishida; Delayed Disruption of Barrier Function in Cultured Human Corneal Epithelial Cells Induced by Tumor Necrosis Factor-α in a Manner Dependent on NF-κB. Invest. Ophthalmol. Vis. Sci. 2008;49(2):565-571. doi: 10.1167/iovs.07-0419.
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purpose. The corneal epithelium provides a barrier that is both important for corneal homeostasis and dependent on tight junctions (TJs) between adjacent epithelial cells. The authors examined the effects of tumor necrosis factor-α (TNF-α), a proinflammatory cytokine, on barrier function and the expression of TJ proteins in simian virus 40–transformed human corneal epithelial (HCE) cells.
methods. The barrier function of cultured HCE cells was evaluated by measurement of transepithelial electrical resistance (TER). The subcellular distribution of the TJ proteins zonula occludens-1 (ZO-1) and occludin and that of the p65 subunit of nuclear factor-κB (NF-κB) were determined by immunofluorescence staining. The expression of ZO-1 and occludin and the phosphorylation and degradation of the NF-κB inhibitory protein IκB-α were examined by immunoblot analysis.
results. TNF-α induced a decrease in the TER of HCE cells in a concentration- and time-dependent manner. It also induced the disappearance of ZO-1 from the interfaces of neighboring HCE cells without affecting the localization of occludin. The abundance of neither ZO-1 nor occludin was affected by TNF-α. TNF-α induced the phosphorylation and downregulation of IκB-α and the translocation of the p65 subunit of NF-κB to the nucleus. The NF-κB inhibitor curcumin blocked the effects of TNF-α on TER and the subcellular localization of ZO-1 at late phase.
conclusions. TNF-α disrupted the barrier function of HCE cells, apparently by affecting the localization of ZO-1 at TJs in a manner dependent on NF-κB at late phase. This action of TNF-α may contribute to the loss of corneal epithelial barrier function associated with ocular inflammation.
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