title: [Molecular mechanism of the disruption of barrier function in cultured human corneal epithelial cells induced by tumor necrosis factor-alpha, a proinflammatory cytokine].
abstract: The corneal epithelium provides a barrier that is important for the maintenance of corneal homeostasis. Tight junctions of the corneal epithelium between adjacent epithelial cells are essential for barrier function. The inflammation or infection around ocular surface has influence on the structure and the function of corneal epithelium. We examined the effects of tumor necrosis factor-alpha (TNF-alpha), a proinflammatory cytokine, on tight junctions as well as on barrier functions in human corneal epithelial (HCE) cells. TNF-alpha reduced the barrier functions of HCE cells in a concentration- and time-dependent manner. It also induced the disappearance of ZO-1 from the interfaces of neighboring cells without affecting their overall abundance. TNF-alpha induced the activation of the NF-kappaB signaling pathway in HCE cells. The NF-kappaB inhibitor curcumin blocked the effects of TNF-alpha on both barrier functions and the subcellular distribution of ZO-1 at a late phase. TNF-alpha induced the redistribution of ZO-1 from TJ of HCE cells and thereby disrupted the barrier function of these cells in a manner dependent on NF-kappaB at the late phase. This action of TNF-alpha may contribute to corneal epithelial damage associated with ocular infection and inflammation.
authors.affiliation: Department of Ocular Pathophysiology, Yamaguchi University Graduate School of Medicine, Yamaguchi-ken, Japan. k.kimura@yamaguchi-u.ac.jp
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kimura
mesh_terms: D002478:Cells, Cultured; D019573:Epithelium, Corneal / Q000473:pathology / Q000502:physiology*; D006801:Humans; D019108:Tight Junctions / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology* / Q000502:physiology
chemical_list: D014409:Tumor Necrosis Factor-alpha