Abstract
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.
Footnotes
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Send reprint requests to: Ki Whan Hong, M.D., Ph.D., Department of Pharmacology, College of Medicine, Pusan National University, 10 Ami-Dong 1-Ga, Seo-Gu, Pusan 602-739, South Korea. E-mail: kwhong{at}hyowon.pusan.ac.kr
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↵1 This study was supported by research funds from Korea Otsuka Pharmaceutical Co. Ltd.
- Abbreviations:
- H/R
- hypoxia/reoxygenation
- ECAM
- endothelial cell adhesion molecule
- ICAM-1
- intercellular adhesion molecule-1
- NF-κB
- nuclear factor-κB
- HUVEC
- human umbilical vein endothelial cell
- fMLP
- formyl-methionyl-leucyl-phenylalanine
- EMSA
- electrophoretic mobility shift assay
- Received January 18, 2000.
- Accepted May 5, 2000.
- The American Society for Pharmacology and Experimental Therapeutics
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