Cilostazol attenuates MCP-1 and MMP-9 expression in vivo in LPS-administrated balloon-injured rabbit aorta and in vitro in LPS-treated monocytic THP-1 cells

Chien Sung Tsai, Feng Yen Lin, Yung Hsiang Chen, Tung Lin Yang, Hsiao Jung Wang, Guo Shine Huang, Chih Yuan Lin, Yi Tin Tsai, Shing Jong Lin, Chi Yuan Li

Research output: Contribution to journalArticle

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Abstract

Monocyte chemoattractant protein-1 (MCP-1) and matrix metalloproteinase-9 (MMP-9) are involved in vascular inflammation. We tested the hypothesis, and explored the underlining mechanisms that cilostazol, a phosphodiesterase 3 inhibitor with antiplatelet and antithrombotic properties, inhibits lipopolysaccharide (LPS)-induced MCP-1 and MMP-9 expression. In a rabbit aorta balloon-injury model, administration of LPS increased macrophage infiltration and MCP-1 and MMP-9 expression; cilostazol supplementation prevented this phenomenon and reduced intimal hyperplasia. In contrast, the reverse zymography showed that cilostazol did not affect TIMP-1 expression in serum. In monocytic THP-1 cells, cilostazol and N6,O2′-dibutyryl-cAMP (dioctanoyl-cAMP, a cAMP analog) dose-dependently inhibited LPS-induced MCP-1 protein expression and MMP-9 activation, but did not affect the tissue inhibitor of metalloproteinase-1. Quantitative real-time polymerase chain reaction (PCR) showed that cilostazol inhibited MCP-1 and MMP-9 mRNA expression. Cilostazol significantly inhibited LPS-induced activation of p38, JNK, and nuclear factor-κB, and the respective inhibitors of p38 and JNK greatly reduced the level of LPS-induced MCP-1 and MMP-9, suggesting the involvement of the p38 and JNK pathways. In conclusion, cilostazol administered with LPS in vivo reduced neointimal hyperplasia and macrophage infiltration in the balloon-injured rabbit aorta; in vitro, cilostazol inhibits LPS-induced MCP-1 and MMP-9 expression. These data suggest that cilostazol may play an important role in preventing endotoxin- and injured-mediated vascular inflammation.

Original languageEnglish
Pages (from-to)54-66
Number of pages13
JournalJournal of Cellular Biochemistry
Volume103
Issue number1
DOIs
Publication statusPublished - Jan 1 2008
Externally publishedYes

Fingerprint

Chemokine CCL2
Balloons
Matrix Metalloproteinase 9
Lipopolysaccharides
Aorta
Rabbits
Tissue Inhibitor of Metalloproteinase-1
Macrophages
Infiltration
Hyperplasia
Blood Vessels
Phosphodiesterase 3 Inhibitors
Chemical activation
Tunica Intima
Inflammation
cilostazol
In Vitro Techniques
MAP Kinase Signaling System
Polymerase chain reaction
Endotoxins

Keywords

  • Cilostazol
  • Inflammation
  • Lipopolysaccharide
  • Matrix metalloproteinase
  • Monocyte chemoattractant protein-1
  • Phosphodiesterase

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

Cite this

Cilostazol attenuates MCP-1 and MMP-9 expression in vivo in LPS-administrated balloon-injured rabbit aorta and in vitro in LPS-treated monocytic THP-1 cells. / Tsai, Chien Sung; Lin, Feng Yen; Chen, Yung Hsiang; Yang, Tung Lin; Wang, Hsiao Jung; Huang, Guo Shine; Lin, Chih Yuan; Tsai, Yi Tin; Lin, Shing Jong; Li, Chi Yuan.

In: Journal of Cellular Biochemistry, Vol. 103, No. 1, 01.01.2008, p. 54-66.

Research output: Contribution to journalArticle

Tsai, Chien Sung ; Lin, Feng Yen ; Chen, Yung Hsiang ; Yang, Tung Lin ; Wang, Hsiao Jung ; Huang, Guo Shine ; Lin, Chih Yuan ; Tsai, Yi Tin ; Lin, Shing Jong ; Li, Chi Yuan. / Cilostazol attenuates MCP-1 and MMP-9 expression in vivo in LPS-administrated balloon-injured rabbit aorta and in vitro in LPS-treated monocytic THP-1 cells. In: Journal of Cellular Biochemistry. 2008 ; Vol. 103, No. 1. pp. 54-66.
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AU - Lin, Feng Yen

AU - Chen, Yung Hsiang

AU - Yang, Tung Lin

AU - Wang, Hsiao Jung

AU - Huang, Guo Shine

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AU - Tsai, Yi Tin

AU - Lin, Shing Jong

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