PMID- 23319318
OWN - NLM
STAT- MEDLINE
DCOM- 20140130
LR  - 20161125
IS  - 1095-8355 (Electronic)
IS  - 1065-6995 (Linking)
VI  - 37
IP  - 1
DP  - 2013 Jan
TI  - Mycophenolic acid regulates spleen tyrosine kinase to repress tumour necrosis 
      factor-alpha-induced monocyte chemotatic protein-1 production in cultured human 
      aortic endothelial cells.
PG  - 19-28
LID - 10.1002/cbin.10003 [doi]
AB  - Atherosclerosis develops from cascades of inflammatory processes. Spleen tyrosine 
      kinase (Syk) and monocyte chemotatic protein-1 (MCP-1) play important roles in 
      the pathogenesis of atherosclerosis. Mycophenolic acid (MPA) has an 
      anti-inflammatory effect. We have investigated whether MPA regulates Syk to 
      repress tumour necrosis factor-alpha (TNF-alpha)-induced MCP-1 production in cultured 
      human aortic endothelial cells. Expression of MCP-1 mRNA and its protein were 
      measured by real time RT-PCR and ELISA, respectively. Reactive oxygen species 
      (ROS) production were measured using 2'7'-dichlorofluorescein diacetate. 
      Activation of AP-1 and NF-kappaB were assessed by electrophoretic mobility shift 
      assay. Tyrosine phosphorylation of Syk was examined by Western blot analysis. 
      TNF-alpha increased MCP-1 at both mRNA and protein levels. TNF-alpha-induced MCP-1 mRNA 
      expression was inhibited by N-acetylcysteine (NAC), Syk inhibitor, Syk-siRNA and 
      MPA. TNF-alpha-induced MCP-1 protein production was also inhibited by Syk inhibitor 
      and MPA. TNF-alpha increased DNA binding activity of AP-1 and NF-kappaB, whereas both 
      AP-1 and NF-kappaB decoy oligodeoxynucleotides downregulated TNF-alpha-induced MCP-1 mRNA 
      expression. TNF-alpha increased ROS generation, which was inhibited by NAC and MPA, 
      but not by Syk inhibitor. TNF-alpha increased tyrosine phosphorylation of Syk, which 
      was attenuated by NAC and MPA. MPA and Syk inhibitor attenuated TNF-alpha-induced DNA 
      binding activity of NF-kappaB and AP-1. TNF-alpha induced MCP-1 expression via activation 
      of AP-1 and NF-kappaB. AP-1 and NF-kappaB were mediated through ROS, followed by Syk. MPA 
      exerts anti-inflammatory effect by inhibiting MCP-1 expression via suppression of 
      ROS and Syk.
CI  - (c) 2012 International Federation for Cell Biology.
FAU - Koo, Tai Yeon
AU  - Koo TY
AD  - Division of Nephrology, Department of Internal Medicine, Asan Medical Center, 
      University of Ulsan, Seoul, Republic of Korea.
FAU - Kim, Yoon Ji
AU  - Kim YJ
FAU - Yang, Won Seok
AU  - Yang WS
FAU - Park, Jung Sik
AU  - Park JS
FAU - Han, Nam Jeong
AU  - Han NJ
FAU - Lee, Joo Mi
AU  - Lee JM
FAU - Park, Su Kil
AU  - Park SK
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20121204
PL  - England
TA  - Cell Biol Int
JT  - Cell biology international
JID - 9307129
RN  - 0 (Anti-Inflammatory Agents)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (NF-kappa B)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.2 (SYK protein, human)
RN  - EC 2.7.10.2 (Syk Kinase)
RN  - HU9DX48N0T (Mycophenolic Acid)
SB  - IM
MH  - Anti-Inflammatory Agents/*pharmacology
MH  - Aorta/cytology/metabolism
MH  - Chemokine CCL2/*biosynthesis
MH  - Endothelial Cells/cytology/*drug effects/metabolism
MH  - Endothelium, Vascular/cytology/metabolism
MH  - Humans
MH  - Intracellular Signaling Peptides and Proteins/*genetics/metabolism
MH  - Mycophenolic Acid/*pharmacology
MH  - NF-kappa B/metabolism
MH  - Protein-Tyrosine Kinases/*genetics/metabolism
MH  - Reactive Oxygen Species/metabolism
MH  - Signal Transduction
MH  - Syk Kinase
MH  - Tumor Necrosis Factor-alpha/antagonists & inhibitors/*genetics/metabolism
EDAT- 2013/01/16 06:00
MHDA- 2014/01/31 06:00
CRDT- 2013/01/16 06:00
PHST- 2012/01/16 00:00 [received]
PHST- 2012/09/14 00:00 [accepted]
PHST- 2013/01/16 06:00 [entrez]
PHST- 2013/01/16 06:00 [pubmed]
PHST- 2014/01/31 06:00 [medline]
AID - 10.1002/cbin.10003 [doi]
PST - ppublish
SO  - Cell Biol Int. 2013 Jan;37(1):19-28. doi: 10.1002/cbin.10003. Epub 2012 Dec 4.