Cilostazol inhibits monocytic cell adhesion to vascular endothelium via upregulation of cAMP.
نویسندگان
چکیده
AIM Cilostazol is clinically used as an inhibitor of platelet aggregation. Although several reports have demonstrated its anti-inflammatory effect, its effect on monocytes and their adhesive interaction to vascular endothelium remains unclear. We thus examined the potential role of cilostazol towards monocyte endothelial interaction under physiological flow conditions. METHODS THP-1 cells, a monocytic cell line, were pretreated with cilostazol (5 microM) for 48 hours. The cells were then perfused over TNF-alpha (5 microg/mL for 4 hours)-stimulated monolayers of human umbilical vein endothelial cells (HUVECs) at shear stress of 1.0 dyen/cm(2). RESULTS TNF-alpha-activated HUVECs supported significantly more monocyte adhesion to HUVECs (7.32+/-1.25/HPF) compared to inactivated HUVECs (0.74+/-0.15/HPF), and the amount of adhesion to TNF-alpha-activated HUVECs was markedly reduced (3.63+/-0.55/HPF) when THP-1 cells were incubated in the presence of cilostazol at 5 microM. Interestingly, surface expressions of integrins were not dramatically changed after cilostazol treatment. Intracellular concentration of cAMP was significantly increased after cilostazol treatment, and treatment with Forskolin and Dibutyryl-cAMP, potent inducers of cAMP, dramatically increased THP-1 adhesion to HUVECs. CONCLUSION These data suggest that cilostazol has a potential anti-inflammatory effect on monocyte-endothelial interactions via the upregulation of intracellular cAMP.
منابع مشابه
Cilostazol protects diabetic rats from vascular inflammation via nuclear factor-kappa B-dependent down-regulation of vascular cell adhesion molecule-1 expression.
Vascular cell adhesion molecule (VCAM)-1 plays a critical role in the initiation and development of vascular inflammation and selective inhibition of adhesion molecules expressed by endothelial cells may present a new therapeutic strategy for the treatment of vascular complications associated with diabetes mellitus. Increasing evidence indicates that cilostazol, a cAMP phosphodiesterase inhibit...
متن کاملCilostazol inhibits oxidative stress-induced premature senescence via upregulation of Sirt1 in human endothelial cells.
OBJECTIVE Cilostazol, a selective inhibitor of PDE3, has a protective effect on endothelium after ischemic vascular damage, through production of nitric oxide (NO). The purpose of the present study was to clarify the molecular mechanisms underlying the preventive effect of treatment with cilostazol on oxidative stress-induced premature senescence in human endothelial cells. METHODS AND RESULT...
متن کاملCilostazol promotes vascular smooth muscles cell differentiation through the cAMP response element-binding protein-dependent pathway.
OBJECTIVE Cilostazol, a potent type 3 phosphodiesterase inhibitor, has recently been found to reduce neointimal formation by inhibiting vascular smooth muscle cell (VSMC) proliferation. The aim of this study is to investigate whether cilostazol exerts an action on phenotypic modulation of VSMCs, another important process in the pathogenesis of neointimal formation. METHODS AND RESULTS Cilosta...
متن کاملPhenyl methimazole inhibits TNF-alpha-induced VCAM-1 expression in an IFN regulatory factor-1-dependent manner and reduces monocytic cell adhesion to endothelial cells.
Proinflammatory cytokine (e.g., TNF-alpha)-induced expression of endothelial cell adhesion molecules (ECAMs) on the lumenal surface of the vascular endothelium and a consequent increase in leukocyte adhesion are key aspects of pathological inflammation. A promising therapeutic approach to diminish aberrant leukocyte adhesion is, therefore, to inhibit cytokine-induced ECAM expression at the tran...
متن کاملHEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Initial accumulation of platelets during arterial thrombus formation in vivo is inhibited by elevation of basal cAMP levels
Platelet accumulation at sites of vascular injury is the primary event in arterial thrombosis. Initial platelet accrual into thrombi is mediated by interactions of platelet adhesion receptors with ligands on the injured endothelium or in the subendothelial matrix. The role of intracellular signals in initial platelet accumulation at sites of endothelial injury, however, is the subject of debate...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Journal of atherosclerosis and thrombosis
دوره 14 5 شماره
صفحات -
تاریخ انتشار 2007