title: Protective effect of dexamethasone against hypoxia-induced disruption of barrier function in human corneal epithelial cells.
abstract: The corneal epithelium functions as a barrier to protect the cornea from external agents such as infectious organisms and toxins and thereby contributes to corneal homeostasis. The barrier function of epithelia is dependent on the formation of tight and adherens junctions between adjacent epithelial cells. We have previously shown that hypoxia disrupts the barrier function of cultured human corneal epithelial (HCE) cells by affecting tight junctions. We have now examined the effect of dexamethasone on this barrier disruption induced by hypoxia in HCE cells. Measurement of transepithelial electrical resistance revealed that the hypoxia-induced decrease in the barrier function of HCE cells was inhibited by dexamethasone in a concentration-dependent manner. The hypoxia-induced loss of the tight junction protein ZO-1 from the borders of adjacent HCE cells (as revealed by immunofluorescence analysis) as well as the hypoxia-induced down-regulation of ZO-1 expression (as revealed by immunoblot analysis) were also inhibited by dexamethasone, whereas this drug had no effect on the expression or distribution of the tight junction protein occludin or of the adherens junction proteins E-cadherin and β-catenin. Moreover, dexamethasone attenuated the reorganization of the actin cytoskeleton, the formation of focal adhesions, and the up-regulation of myosin light chain kinase expression induced by hypoxia in HCE cells. Our results thus suggest that dexamethasone protects corneal epithelial cells from the hypoxia-induced disruption of barrier function by maintaining the distribution and expression of ZO-1 as well as the organization of the actin cytoskeleton.
authors.affiliation: Department of Ophthalmology, Yamaguchi University School of Medicine, 1-1-1 Minami-Kogushi, Ube, Yamaguchi 755-8505, Japan. k.kimura@yamaguchi-u.ac.jp
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kimura
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Teranishi
authors.forename: Koji
authors.initials: K
authors.lastname: Kawamoto
authors.forename: Teruo
authors.initials: T
authors.lastname: Nishida
mesh_terms: D000199:Actins / Q000378:metabolism; D022005:Adherens Junctions / Q000187:drug effects* / Q000378:metabolism; D015820:Cadherins / Q000378:metabolism; D002461:Cell Line, Transformed; D002463:Cell Membrane Permeability / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D017097:Electric Impedance; D019573:Epithelium, Corneal / Q000187:drug effects* / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D005938:Glucocorticoids / Q000494:pharmacology*; D006801:Humans; D000860:Hypoxia / Q000378:metabolism*; D015151:Immunoblotting; D008565:Membrane Proteins / Q000378:metabolism; D062793:Occludin; D010750:Phosphoproteins / Q000378:metabolism; D019108:Tight Junctions / Q000187:drug effects* / Q000378:metabolism; D062826:Zonula Occludens-1 Protein; D051176:beta Catenin / Q000378:metabolism
chemical_list: D000199:Actins; D015820:Cadherins; D005938:Glucocorticoids; D008565:Membrane Proteins; C568985:OCLN protein, human; D062793:Occludin; D010750:Phosphoproteins; C569042:TJP1 protein, human; D062826:Zonula Occludens-1 Protein; D051176:beta Catenin; D003907:Dexamethasone