These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Cilostazol reduces MCP-1-induced chemotaxis and adhesion of THP-1 monocytes by inhibiting CCR2 gene expression.
    Author: Chuang SY, Yang SH, Pang JH.
    Journal: Biochem Biophys Res Commun; 2011 Jul 29; 411(2):402-8. PubMed ID: 21756880.
    Abstract:
    The chemotaxis and adhesion of monocytes to the injured endothelium in the early atherosclerosis is important. Cilostazol, a specific phosphodiesterase type III inhibitor, is known to exhibit anti-atherosclerotic effects mediated by different mechanisms. This study aimed to investigate the modulating effect of cilostazol on the MCP-1-induced chemotaxis and adhesion of monocytes. The gene expression of CCR2, the major receptor of MCP-1 in THP-1 monocytes, was also analyzed. The chemotaxis of monocytes toward MCP-1 was investigated using the transwell filter assay. Cilostazol dose-dependently inhibited the MCP-1-induced chemotaxis of monocytes which was shown to be cAMP-dependent. Using western blot analysis and flow cytometry method, we demonstrated the decrease of CCR2 protein at the cell membrane of monocytes by cilostazol treatment. Results from RT/real-time PCR confirmed the decrease of CCR2 mRNA expression by cilostazol which was also mediated by cAMP. Similar inhibition was also noted in human peripheral monocytes. The post-CCR2 signaling pathways including p44/42 and p38 MAPK were examined by western blot analysis. Result confirmed the inhibitory effect of cilostazol on the phosphorylation of p44/42 and p38 MAPK after MCP-1 stimulation. The activation of monocytes after MCP-1 treatment exhibited enhanced adhesion to vascular endothelial cells which was dose-dependently suppressed by cilostazol. Together, cilostazol was demonstrated, for the first time, to inhibit the CCR2 gene expression and MCP-1-induced chemotaxis and adhesion of monocytes which might therefore reduce the infiltration of monocytes during the early atherosclerosis. The present study provides an additional molecular mechanism underlying the anti-atherosclerotic effects of cilostazol.
    [Abstract] [Full Text] [Related] [New Search]