Vol. 294, Issue 3, 864-869, September 2000

Rebamipide Inhibits Neutrophil Adhesion to Hypoxia/Reoxygenation-Stimulated Endothelial Cells via Nuclear Factor-B-Dependent Pathway¹

Chi Dae Kim , Yong Ki Kim, So Hyun Lee and Ki Whan Hong

Departments of Pharmacology (C.D.K., S.H.L., K.W.H), Internal Medicine (Y.K.K.), and Research Center for Molecular Medicine (C.D.K.), College of Medicine, Pusan National University, Pusan, Korea

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-B 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 × 10⁴ counts × 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-B 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.