PMID- 20128801
OWN - NLM
STAT- MEDLINE
DCOM- 20100712
LR  - 20240109
IS  - 1476-5381 (Electronic)
IS  - 0007-1188 (Print)
IS  - 0007-1188 (Linking)
VI  - 159
IP  - 6
DP  - 2010 Mar
TI  - Cilostazol is anti-inflammatory in BV2 microglial cells by inactivating nuclear 
      factor-kappaB and inhibiting mitogen-activated protein kinases.
PG  - 1274-85
LID - 10.1111/j.1476-5381.2009.00615.x [doi]
AB  - BACKGROUND AND PURPOSE: Cilostazol is a specific inhibitor of 3'-5'-cyclic 
      adenosine monophosphate (cAMP) phosphodiesterase, which is widely used to treat 
      ischemic symptoms of peripheral vascular disease. Although cilostazol has been 
      shown to exhibit vasodilator properties as well as antiplatelet and 
      anti-inflammatory effects, its cellular mechanism in microglia is unknown. In the 
      present study, we assessed the anti-inflammatory effect of cilostazol on the 
      production of pro-inflammatory mediators in lipopolysaccharide (LPS)-stimulated 
      murine BV2 microglia. EXPERIMENTAL APPROACH: We examined the effects of 
      cilostazol on LPS-induced nuclear factor-kappaB (NF-kappaB) activation and 
      phosphorylation of mitogen-activated protein kinases (MAPKs). KEY RESULTS: 
      Cilostazol suppressed production of nitric oxide (NO), prostaglandin E(2) 
      (PGE(2)) and the proinflammatory cytokines, interleukin-1 (IL-1), tumour necrosis 
      factor-alpha, and monocyte chemoattractant protein-1 (MCP-1), in a 
      concentration-dependent manner. Inhibitory effects of cilostazol were not 
      affected by treatment with an adenylate cyclase inhibitor, SQ 22536, indicating 
      that these actions of cilostazol were cAMP-independent. Cilostazol significantly 
      inhibited the DNA binding and transcriptional activity of NF-kappaB. Moreover, 
      cilostazol blocked signalling upstream of NF-kappaB activation by inhibiting 
      extracellular signal-regulated kinases 1 and 2 (ERK1/2) and c-Jun N-terminal 
      kinase (JNK), but without affecting the activity of p38 MAPK. CONCLUSION AND 
      IMPLICATIONS: Our results demonstrate that suppression of the NF-kappaB, ERK, JNK 
      signalling pathways may inhibit LPS-induced NO and PGE(2) production. Therefore, 
      cilostazol may have therapeutic potential for neurodegenerative diseases by 
      inhibiting pro-inflammatory mediators and cytokine production in activated 
      microglia.
FAU - Jung, Won-Kyo
AU  - Jung WK
AD  - Department of Marine Life Science, Chosun University, Gwangju, Republic of Korea.
FAU - Lee, Da-Young
AU  - Lee DY
FAU - Park, Cheol
AU  - Park C
FAU - Choi, Yung Hyun
AU  - Choi YH
FAU - Choi, Inhak
AU  - Choi I
FAU - Park, Sae-Gwang
AU  - Park SG
FAU - Seo, Su-Kil
AU  - Seo SK
FAU - Lee, Soo-Woong
AU  - Lee SW
FAU - Yea, Sung Su
AU  - Yea SS
FAU - Ahn, Soon-Cheol
AU  - Ahn SC
FAU - Lee, Chang-Min
AU  - Lee CM
FAU - Park, Won Sun
AU  - Park WS
FAU - Ko, Jae-Hong
AU  - Ko JH
FAU - Choi, Il-Whan
AU  - Choi IW
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20100128
PL  - England
TA  - Br J Pharmacol
JT  - British journal of pharmacology
JID - 7502536
RN  - 0 (Anti-Inflammatory Agents, Non-Steroidal)
RN  - 0 (Inflammation Mediators)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (NF-kappa B)
RN  - 0 (Tetrazoles)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - E0399OZS9N (Cyclic AMP)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - K7Q1JQR04M (Dinoprostone)
RN  - N7Z035406B (Cilostazol)
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents, Non-Steroidal/*pharmacology
MH  - Blotting, Western
MH  - Cell Line
MH  - Cell Survival/drug effects
MH  - Cilostazol
MH  - Cyclic AMP/metabolism
MH  - Dinoprostone/biosynthesis
MH  - Dose-Response Relationship, Drug
MH  - Electrophoretic Mobility Shift Assay
MH  - Inflammation Mediators/immunology/metabolism
MH  - Lipopolysaccharides/pharmacology
MH  - Mice
MH  - Microglia/*drug effects/enzymology/immunology/metabolism
MH  - Microscopy, Confocal
MH  - Mitogen-Activated Protein Kinases/*antagonists & inhibitors
MH  - NF-kappa B/*antagonists & inhibitors
MH  - Nitric Oxide/biosynthesis
MH  - Phosphorylation
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Signal Transduction
MH  - Tetrazoles/*pharmacology
PMC - PMC2848931
EDAT- 2010/02/05 06:00
MHDA- 2010/07/14 06:00
PMCR- 2011/03/01
CRDT- 2010/02/05 06:00
PHST- 2010/02/05 06:00 [entrez]
PHST- 2010/02/05 06:00 [pubmed]
PHST- 2010/07/14 06:00 [medline]
PHST- 2011/03/01 00:00 [pmc-release]
AID - BPH615 [pii]
AID - 10.1111/j.1476-5381.2009.00615.x [doi]
PST - ppublish
SO  - Br J Pharmacol. 2010 Mar;159(6):1274-85. doi: 10.1111/j.1476-5381.2009.00615.x. 
      Epub 2010 Jan 28.