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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
Author(s) -
Tsai ChienSung,
Lin FengYen,
Chen YungHsiang,
Yang TungLin,
Wang HsiaoJung,
Huang GuoShine,
Lin ChihYuan,
Tsai YiTin,
Lin ShingJong,
Li ChiYuan
Publication year - 2007
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.21388
Subject(s) - cilostazol , p38 mitogen activated protein kinases , monocyte , lipopolysaccharide , chemistry , in vivo , inflammation , intimal hyperplasia , pharmacology , medicine , endocrinology , biology , signal transduction , mapk/erk pathway , aspirin , biochemistry , microbiology and biotechnology , smooth muscle
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. J. Cell. Biochem. 103: 54–66, 2008. © 2007 Wiley‐Liss, Inc.