Abstract
Purpose:
Dry eye causes the tear hyperosmolality which stimulates an inflammatory cascade and disrupts corneal barrier function. Rebamipide which has mucin secretagogue activity is used for the treatment of dry eye in Japan. This study examined the effects of rebamipide on barrier function and cytokine expression in a human corneal epithelial (HCE) cell line.
Methods:
Barrier function of HCE cells was evaluated by measurement of transepithelial electrical resistance. The subcellular localization of the tight-junction protein zona occludens (ZO)-1 was examined by immunofluorescence analysis. The release of cytokines was determined with enzyme-linked immunosorbent assays, and the intracellular abundance of cytokine mRNAs was quantitated by reverse transcription and real-time polymerase chain reaction analysis. Degradation of the NF-κB inhibitor IκBα was detected by immunoblot analysis.
Results:
Rebamipide increased barrier function of HCE cells in a concentration-dependent manner as well as blocked both the loss of barrier function and the disappearance of ZO-1 from the cell surface induced by tumor necrosis factor (TNF)-α or IL-1β. Rebamipide also suppressed cytokine-induced expression of interleukin-6 and interleukin-8 at the mRNA and protein levels as well as inhibited the TNF-α-induced degradation of IκBα.
Conclusions:
Together with its mucin secretagogue activity, rebamipide is effective for the treatment of dry eye thorough the mechanism by up-regulation of barrier function and anti-inflammatory effects.
Keywords: 486 cornea: tears/tear film/dry eye •
503 drug toxicity/drug effects •
490 cytokines/chemokines