TY - JOUR T1 - Rebamipide Inhibits Neutrophil Adhesion to Hypoxia/Reoxygenation-Stimulated Endothelial Cells via Nuclear Factor-κB-Dependent Pathway JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 864 LP - 869 VL - 294 IS - 3 AU - Chi Dae Kim AU - Yong Ki Kim AU - So Hyun Lee AU - Ki Whan Hong Y1 - 2000/09/01 UR - http://jpet.aspetjournals.org/content/294/3/864.abstract N2 - This study was designed to determine whether rebamipide can inhibit neutrophil adhesion to human umbilical vein endothelial cells (HUVECs) stimulated with 1 h of hypoxia followed by 4 h of reoxygenation (H/R). Furthermore, to define the action mechanisms, we determined the effect of rebamipide on the surface expression of endothelial cell adhesion molecules E-selectin, P-selectin, and intercellular adhesion molecule-1 (ICAM-1) on H/R-stimulated HUVECs. Under resting conditions, both E-selectin and P-selectin were not expressed on the surface of HUVECs in contrast to ICAM-1, which was constitutively expressed. After stimulation with H/R, HUVECs showed an enhanced neutrophil adhesivity in association with an increased surface expression of E-selectin and P-selectin with a marginal increase in ICAM-1 expression. In parallel, the increased nuclear translocation of nuclear factor-κB in H/R-stimulated HUVECs was monitored by electrophoretic mobility shift assay (adjusted volume units, 11.9 ± 2.5 × 104 counts × mm2 in unstimulated cells versus 24.2 ± 3.0 × 104counts × mm2 in H/R-stimulated cells). Rebamipide suppressed the surface expression of E-selectin and P-selectin with a subsequent inhibition of neutrophil adhesion to H/R-stimulated HUVECs. In line with these results, rebamipide (100, 300, and 1000 μM) inhibited H/R-induced nuclear translocation of nuclear factor-κB in a concentration-dependent manner. Taken together, this study demonstrates that rebamipide inhibits neutrophil adhesion to HUVECs by a mechanism involving inhibition of transcription-dependent surface expression of E-selectin and P-selectin in H/R-stimulated endothelial cells. The American Society for Pharmacology and Experimental Therapeutics ER -