PMID- 18703532
OWN - NLM
STAT- MEDLINE
DCOM- 20090410
LR  - 20211203
IS  - 1755-3245 (Electronic)
IS  - 0008-6363 (Linking)
VI  - 81
IP  - 1
DP  - 2009 Jan 1
TI  - Cilostazol inhibits cytokine-induced nuclear factor-kappaB activation via 
      AMP-activated protein kinase activation in vascular endothelial cells.
PG  - 133-9
LID - 10.1093/cvr/cvn226 [doi]
AB  - AIMS: Cilostazol is a selective inhibitor of phosphodiesterase 3 that increases 
      intracellular cyclic AMP (cAMP) levels and activates protein kinase A, thereby 
      inhibiting platelet aggregation and inducing peripheral vasodilation. We 
      hypothesized that cilostazol may prevent inflammatory cytokine induced-nuclear 
      factor (NF)-kappaB activation by activating AMP-activated protein kinase (AMPK) 
      in vascular endothelial cells. METHODS AND RESULTS: Cilostazol was observed to 
      activate AMPK and its downstream target, acetyl-CoA carboxylase, in human 
      umbilical vein endothelial cells (HUVEC). Phosphorylation of AMPK with cilostazol 
      was not affected by co-treatment with an adenylate cyclase inhibitor, SQ 22536, 
      and a cell-permeable cAMP analogue, pCTP-cAMP, did not induce AMPK 
      phosphorylation and had no effect on cilostazol-induced AMPK phosphorylation, 
      suggesting that cilostazol-induced AMPK activation occurs through a signalling 
      pathway independent of cyclic AMP. Cilostazol also dose-dependently inhibited 
      tumour necrosis factor alpha (TNFalpha)-induced NF-kappaB activation and 
      TNFalpha-induced I kappa B kinase activity. Furthermore, cilostazol attenuated 
      the TNFalpha-induced gene expression of various pro-inflammatory and cell 
      adhesion molecules, such as vascular cell adhesion molecule-1, E-selectin, 
      intercellular adhesion molecule-1, monocyte chemoattractant protein-1 (MCP-1), 
      and PECAM-1 in HUVEC. RNA interference of AMPK alpha 1 or the AMPK inhibitor 
      compound C attenuated cilostazol-induced inhibition of NF-kappaB activation by 
      TNFalpha. CONCLUSION: In the light of these findings, we suggest that cilostazol 
      might attenuate the cytokine-induced expression of adhesion molecule genes by 
      inhibiting NF-kappaB following AMPK activation.
FAU - Hattori, Yoshiyuki
AU  - Hattori Y
AD  - Department of Endocrinology and Metabolism, Dokkyo University School of Medicine, 
      Mibu, Tochigi 321-0293, Japan.
FAU - Suzuki, Kunihiro
AU  - Suzuki K
FAU - Tomizawa, Atsuko
AU  - Tomizawa A
FAU - Hirama, Noriko
AU  - Hirama N
FAU - Okayasu, Toshie
AU  - Okayasu T
FAU - Hattori, Sachiko
AU  - Hattori S
FAU - Satoh, Hiroko
AU  - Satoh H
FAU - Akimoto, Kazumi
AU  - Akimoto K
FAU - Kasai, Kikuo
AU  - Kasai K
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Retracted Publication
DEP - 20080814
PL  - England
TA  - Cardiovasc Res
JT  - Cardiovascular research
JID - 0077427
RN  - 0 (CCL2 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (E-Selectin)
RN  - 0 (I-kappa B Proteins)
RN  - 0 (NF-kappa B)
RN  - 0 (NFKBIA protein, human)
RN  - 0 (Phosphodiesterase Inhibitors)
RN  - 0 (Platelet Endothelial Cell Adhesion Molecule-1)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tetrazoles)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (Vascular Cell Adhesion Molecule-1)
RN  - 126547-89-5 (Intercellular Adhesion Molecule-1)
RN  - 139874-52-5 (NF-KappaB Inhibitor alpha)
RN  - E0399OZS9N (Cyclic AMP)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.11.3 (AMP-Activated Protein Kinase Kinases)
RN  - N7Z035406B (Cilostazol)
SB  - IM
RIN - Cardiovasc Res. 2011 Oct 1;92(1):181. PMID: 21917991
MH  - AMP-Activated Protein Kinase Kinases
MH  - Cells, Cultured
MH  - Chemokine CCL2/metabolism
MH  - Cilostazol
MH  - Cyclic AMP/metabolism
MH  - Dose-Response Relationship, Drug
MH  - E-Selectin/metabolism
MH  - Endothelium, Vascular/cytology/*drug effects/*metabolism
MH  - Humans
MH  - I-kappa B Proteins/metabolism
MH  - Intercellular Adhesion Molecule-1/metabolism
MH  - NF-KappaB Inhibitor alpha
MH  - NF-kappa B/*metabolism
MH  - Phosphodiesterase Inhibitors/*pharmacology
MH  - Platelet Endothelial Cell Adhesion Molecule-1/metabolism
MH  - Protein Kinases/*metabolism
MH  - RNA, Messenger/metabolism
MH  - Tetrazoles/*pharmacology
MH  - Tumor Necrosis Factor-alpha/*metabolism
MH  - Umbilical Veins/cytology
MH  - Vascular Cell Adhesion Molecule-1/metabolism
EDAT- 2008/08/16 09:00
MHDA- 2009/04/11 09:00
CRDT- 2008/08/16 09:00
PHST- 2008/08/16 09:00 [entrez]
PHST- 2008/08/16 09:00 [pubmed]
PHST- 2009/04/11 09:00 [medline]
AID - cvn226 [pii]
AID - 10.1093/cvr/cvn226 [doi]
PST - ppublish
SO  - Cardiovasc Res. 2009 Jan 1;81(1):133-9. doi: 10.1093/cvr/cvn226. Epub 2008 Aug 
      14.