Effects of aPhosphodiesterase 3 inhibitor, cilostazol on soluble adhesion molecules release from TNF-α-stimulated human umbilical endothelial cells
LUO Jing-Hui, LIN Yong-Cheng, CHEN Zhi-LIang, WATANABE Hiroshi, OZEKI Mariko, HAYASHI Hideharu
2003, 8(6):
621-626.
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AIM: To examine the effects of cilostazol,a novel selectivePhosphodiesterase type 3 inhibitor,on soluble cell adhesion molecules(sCAMs)released from tumor necrosis factor-α(TNF-α)-stimulated human umbilical endothelial cells(HUVECs),and to investigate thePossible mechanisms of these effects of cilostazol.METHODS: Confluent HUVECs between 4-6Passages were used and stimulated by TNF-α(10μg·L-1)with or without coincubation of cilostazol(1 -10μmol·L-1)for 24 h.Soluble vascular cell adhesion molecule-1(sVCAM-1),soluble intercellular adhesion molecule-1(sICAM-1)and soluble endothelialleukocyte adhesion molecule-1(sELAM-1,sE-selectin)in cell culture medium were measured by ELISA,and availability of cells was detected by MTT assay.RESULTS: Cilostazol(1 -10μmol·L-1)did not affect sICAM-1 and sE-selectin released from HUVECs,but in contrast,it significantly inhibited theProduction of TNF-α-induced sVCAM-1,and this effect was canceled bylω-nitro-L-arginine methyl ester(lω-NAME,0.1μmol·L-1),a nonselective nitro oxide synthase(NOS)inhibitor.MTT assay indicated that the treatment of HUVECs with cilostazol(1 -30μmol·L-1)for 24 h affected cell availability in a complexPattern.It was increased at alow dose of cilostazol(1μmol·L-1),but it was decreased at a relatively high dosage,30μmol·L-1.And at the medium dosage of cilostazol,10μmol·L-1,cell availability was almost unaffected.CONCLUSIONS: Cilostazol significantly inhibits sVCAM-1 released from TNF-α-activated HUVECs,and the effect on cytokine-challenged endothelial cells might have some relationshiPwith activating NOS,andPossibly,it is via a NO-dependentPathway.ThePresent result suggests that cilostazolPartially eliminates some of the adherent reactions of HUVECs to TNF-α,a deleterious cytokine,and to some extent,it might have thePotential toPrevent atherosclerosis and other cardiovascular diseases.
