PMID- 17516547
OWN - NLM
STAT- MEDLINE
DCOM- 20080229
LR  - 20181201
IS  - 0730-2312 (Print)
IS  - 0730-2312 (Linking)
VI  - 103
IP  - 1
DP  - 2008 Jan 1
TI  - 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.
PG  - 54-66
AB  - 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-kappaB, 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.
CI  - Copyright (c) 2007 Wiley-Liss, Inc.
FAU - Tsai, Chien-Sung
AU  - Tsai CS
AD  - Division of Cardiovascular Surgery, Tri-service General Hospital, National 
      Defense Medical Center, Taipei, Taiwan.
FAU - Lin, Feng-Yen
AU  - Lin FY
FAU - Chen, Yung-Hsiang
AU  - Chen YH
FAU - Yang, Tung-Lin
AU  - Yang TL
FAU - Wang, Hsiao-Jung
AU  - Wang HJ
FAU - Huang, Guo-Shine
AU  - Huang GS
FAU - Lin, Chih-Yuan
AU  - Lin CY
FAU - Tsai, Yi-Tin
AU  - Tsai YT
FAU - Lin, Shing-Jong
AU  - Lin SJ
FAU - Li, Chi-Yuan
AU  - Li CY
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Cell Biochem
JT  - Journal of cellular biochemistry
JID - 8205768
RN  - 0 (Chemokine CCL2)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (NF-kappa B)
RN  - 0 (Tetrazoles)
RN  - 0 (Transcription Factor AP-1)
RN  - E0399OZS9N (Cyclic AMP)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
RN  - N7Z035406B (Cilostazol)
SB  - IM
MH  - Animals
MH  - Aorta/*drug effects/injuries/*metabolism
MH  - Catheterization
MH  - Cell Line
MH  - Chemokine CCL2/genetics/*metabolism
MH  - Chemotaxis/drug effects
MH  - Cilostazol
MH  - Cyclic AMP/biosynthesis
MH  - Cytoprotection/drug effects
MH  - Gene Expression Regulation/drug effects
MH  - Humans
MH  - Lipopolysaccharides/*administration & dosage
MH  - Male
MH  - Matrix Metalloproteinase 9/genetics/*metabolism
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - Monocytes/cytology/drug effects/*metabolism
MH  - NF-kappa B/metabolism
MH  - Rabbits
MH  - Tetrazoles/*pharmacology
MH  - Transcription Factor AP-1/metabolism
EDAT- 2007/05/23 09:00
MHDA- 2008/03/01 09:00
CRDT- 2007/05/23 09:00
PHST- 2007/05/23 09:00 [pubmed]
PHST- 2008/03/01 09:00 [medline]
PHST- 2007/05/23 09:00 [entrez]
AID - 10.1002/jcb.21388 [doi]
PST - ppublish
SO  - J Cell Biochem. 2008 Jan 1;103(1):54-66. doi: 10.1002/jcb.21388.