Cilostazol, a cAMP Phosphodiesterase Inhibitor, Attenuates the Production of Monocyte Chemoattractant protein-1 in Response to Tumor Necrosis Factor-α in Vascular Endothelial Cells

Abstract

The induction of monocyte chemoattractant protein-1 (MCP-1) in vascular endothelial cells is thought to be an initial event in the development of atherosclerotic lesions. Therefore, inhibition of MCP-1 production may exhibit some effects in preventing atherosclerosis. In the present study, we found that 10 µM cilostazol, a cAMP phosphodiesterase inhibitor, increased the intracellular cAMP content by a twenty-five times of the basal level and resulted in the reduction of basal MCP-1 release by 41% from 168 ± 11 ng/24 hr/mg protein to 99 ± 14 ng/24 hr/mg protein (P < 0.001) from cultured human umbilical vein endothelial cells. Furthermore, 10 µM cilostazol also significantly attenuated the dose-dependent increment of MCP-1 production by tumor necrosis factor-α. The inhibition was consistent with the reduction of MCP-1 mRNA level, possibly through reduced activation of transcription factor NF-κB level. Similarly, 1 mM dibutyryl cAMP inhibited MCP-1 production in endothelial cells. These data suggest that cilostazol inhibits MCP-1 production through increased intracellular cAMP levels and modulation of its expression in vascular endothelial cells.

Key words

Monocyte Chemoattractant Protein-1 - Cyclic AMP - Endothelial Cells - NF-κB - Phosphodiesterase Inhibitor