Rebamipide inhibits neutrophil adhesion to hypoxia/reoxygenation-stimulated endothelial cells via nuclear factor-kappaB-dependent pathway.
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-kappaB in H/R-stimulated HUVECs was monitored by electrophoretic mobility shift assay (adjusted volume units, 11.9 +/- 2.5 x 10(4) counts x mm(2) in unstimulated cells versus 24.2 +/- 3.0 x 10(4) counts x mm(2) 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 microM) inhibited H/R-induced nuclear translocation of nuclear factor-kappaB 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.
Kim
C D
CD
Department of Pharmacology, College of Medicine, Pusan National University, Korea.
Kim
Y K
YK
Lee
S H
SH
Hong
K W
KW
D000409:Alanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology*; D002448:Cell Adhesion; D015687:Cell Hypoxia; D002478:Cells, Cultured; D019040:E-Selectin / Q000276:immunology / Q000378:metabolism; D004730:Endothelium, Vascular / Q000166:cytology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology / Q000378:metabolism; D016328:NF-kappa B / Q000502:physiology*; D009504:Neutrophils / Q000502:physiology*; D019007:P-Selectin / Q000276:immunology / Q000378:metabolism; D015363:Quinolones / Q000494:pharmacology*; D014471:Umbilical Veins / Q000166:cytology
D000911:Antibodies, Monoclonal; D000975:Antioxidants; D019040:E-Selectin; D016328:NF-kappa B; D019007:P-Selectin; D015363:Quinolones; D018799:Intercellular Adhesion Molecule-1; C052785:rebamipide; D000409:Alanine