کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
5829957 | 1559012 | 2011 | 8 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Cilostazol inhibits matrix invasion and modulates the gene expressions of MMP-9 and TIMP-1 in PMA-differentiated THP-1 cells
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب سلولی و مولکولی
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چکیده انگلیسی
The invasion of monocytes into the subendothelium space plays an important role in the early stage of atherosclerosis. Cilostazol, a specific phosphodiesterase type III (PDE3) inhibitor, has been shown to exhibit anti-atherosclerotic effect. The present study aimed to investigate the modulating effects of cilostazol on monocyte invasion and the gene expressions of matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) in phorbol 12-myristate 13-acetate (PMA)-differentiated THP-1. We found that PMA significantly increased the invasive ability and the MMP-9 activity of THP-1 cells, as analyzed by matrix invasion assay and gelatin zymography, respectively. The increased expression of MMP-9 was demonstrated at both the RNA and protein levels by RT/real-time PCR and western blot analysis. These changes were markedly inhibited by cilostazol in a dose-dependent manner, which also could be observed when cAMP analog was used. On the contrary, the expression of TIMP-1, an inhibitor of MMP-9, was significantly upregulated by cilostazol dose dependently at both the RNA and protein levels. Reverse zymography further confirmed the increase of TIMP-1 activity after cilostazol treatment. The increase of TIMP-1 by cilostazol, however, was not cAMP-dependent. Cilostazol reduced the MMP-9 promoter activity and suppressed the nuclear translocation of NF-κB, indicating that the inhibitory effect of cilostazol is at the transcriptional level. In conclusion, the present study provides an additional mechanism underlying the anti-atherosclerotic effect of cilostazol by inhibiting the monocyte invasion and modulating the gene expressions of MMP-9 and TIMP-1 in monocytes upon differentiating to macrophages.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Pharmacology - Volume 670, Issues 2â3, 30 November 2011, Pages 419-426
Journal: European Journal of Pharmacology - Volume 670, Issues 2â3, 30 November 2011, Pages 419-426
نویسندگان
Shih-Yi Chuang, Su-Hui Yang, Tzi-Ya Chen, Jong-Hwei S. Pang,