Effects of cilostazol on LPS-stimulated adhesion and soluble adherent molecules release / 中国药理学通报

ABSTRACT

AIM To examine the effect of cilostazol, a no vel selective phosphodiesterase type 3 inhibitor, on adherence between neutrophils and human umbilical e ndothelial cells ( HUVECs ) and investigate its possible mechanisms. MET HODS Confluent HUVECs between 4～6 passages were used and stimulated by l ipopolysaccharide (LPS, 5 mg?L -1 ) with or without coincubation of cilosta zol (1～10 ?mol?L -1 ) for 24 h. Soluble cell adhesion molecules (sCAMs), including vascular cell adhesion molecule-1 (sVCAM-1), intercellular adhesion molecule-1 (sICAM-1) and endothelial leukocyte adhesion molecule-1 (sELAM-1, sE-selectin) in cell culture medium were measured by ELISA. RESULTS Cilostazol (1～10 ?mol?L -1 ) inhibited adherence between neutrophils and HUVECs in a dose- dependent manor. At the same time, cilostazol didn't affect sICAM-1 and sE-sel ectin release from LPS-stimulated HUVECs, but in contrast, it significantly inh ibited sVCAM-1 production under the same experiment condition, and this effect was canceled by H-89, an inhibitor of protein kinase A ( PKA ). CONCLUS ION Cilostazol significantly inhibits adherence between neutrophils and H UVECs, and downregulates sVCAM-1 release from LPS-activated HUVECs, and these effects on cytokine-challenged endothelial cells might be via a PKA-dependent pathway. The present result suggests that cilostazol partially eliminates some o f the adherent reactions of HUVECs to LPS, a deleterious cytokine, and it is rea sonable to consider that cilostazol might be a strategy for preventing atheroscl erosis and other cardiovascular diseases.