PMID- 15191888
OWN - NLM
STAT- MEDLINE
DCOM- 20041109
LR  - 20200930
IS  - 0363-6135 (Print)
IS  - 0363-6135 (Linking)
VI  - 287
IP  - 4
DP  - 2004 Oct
TI  - Sphingosine kinase-1 mediates TNF-alpha-induced MCP-1 gene expression in 
      endothelial cells: upregulation by oscillatory flow.
PG  - H1452-8
AB  - Atherosclerosis is a focal inflammatory disease and preferentially occurs in 
      areas of low fluid shear stress and oscillatory flow, whereas the risk of 
      atherosclerosis is decreased in regions of high fluid shear stress and steady 
      laminar flow. Sphingosine kinase-1 (SphK1) catalyzes the conversion of 
      sphingosine to sphingosine-1 phosphate (S1P), a sphingolipid metabolite that 
      plays important roles in angiogenesis, inflammation, and cell growth. In the 
      present study, we demonstrated that exposure of human aortic endothelial cells to 
      oscillatory flow (shear stress, +/-5 dyn/cm(2) for 48 h) resulted in a marked 
      increase in SphK1 mRNA levels compared with endothelial cells kept in static 
      culture. In contrast, laminar flow (shear stress, 20 dyn/cm(2) for 48 h) 
      decreased SphK1 mRNA levels. We further investigated the role of SphK1 in 
      TNF-alpha-induced expression of inflammatory genes, such as monocyte 
      chemoattractant protein-1 (MCP-1) and VCAM-1 by using small interfering RNA 
      (siRNA) specifically for SphK1. Treatment of endothelial cells with SphK1 siRNA 
      suppressed TNF-alpha-induced increase in MCP-1 mRNA levels, MCP-1 protein 
      secretion, and activation of p38 MAPK. SphK1 siRNA also inhibited 
      TNF-alpha-induced cell surface expression of VCAM-1, but not ICAM-1, protein. 
      Exposure of endothelial cells to S1P led to an increase in MCP-1 protein 
      secretion and MCP-1 mRNA levels and activation of NF-kappaB-mediated 
      transcriptional activity. Treatment of endothelial cells with the p38 MAPK 
      inhibitor SB-203580 suppressed S1P-induced MCP-1 protein secretion. These data 
      suggest that SphK1 mediates TNF-alpha-induced MCP-1 gene expression through a p38 
      MAPK-dependent pathway and may participate in oscillatory flow-mediated 
      proinflammatory signaling pathway in the vasculature.
FAU - Chen, Xi-Lin
AU  - Chen XL
AD  - Discovery Research, AtheroGenics, Inc., 8995 Westside Parkway, Alpharetta, GA 
      30004, USA. xchen@atherogenics.com
FAU - Grey, Janice Y
AU  - Grey JY
FAU - Thomas, Suzanne
AU  - Thomas S
FAU - Qiu, Fei-Hua
AU  - Qiu FH
FAU - Medford, Russell M
AU  - Medford RM
FAU - Wasserman, Martin A
AU  - Wasserman MA
FAU - Kunsch, Charles
AU  - Kunsch C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20040610
PL  - United States
TA  - Am J Physiol Heart Circ Physiol
JT  - American journal of physiology. Heart and circulatory physiology
JID - 100901228
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Chemokine CCL2)
RN  - 0 (NF-kappa B)
RN  - 0 (RNA, Messenger)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - EC 2.7.1.- (Phosphotransferases (Alcohol Group Acceptor))
RN  - EC 2.7.1.- (sphingosine kinase)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Antineoplastic Agents/*pharmacology
MH  - Aorta/cytology
MH  - Arteriosclerosis/immunology/metabolism/physiopathology
MH  - Cells, Cultured
MH  - Chemokine CCL2/*genetics/metabolism
MH  - Endothelium, Vascular/cytology/metabolism/*physiology
MH  - Humans
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - NF-kappa B/metabolism
MH  - Phosphotransferases (Alcohol Group Acceptor)/*metabolism
MH  - Promoter Regions, Genetic/physiology
MH  - RNA, Messenger/metabolism
MH  - RNA, Small Interfering
MH  - Signal Transduction/drug effects/immunology
MH  - Stress, Mechanical
MH  - Tumor Necrosis Factor-alpha/*pharmacology
MH  - Up-Regulation
MH  - p38 Mitogen-Activated Protein Kinases
EDAT- 2004/06/12 05:00
MHDA- 2004/11/13 09:00
CRDT- 2004/06/12 05:00
PHST- 2004/06/12 05:00 [pubmed]
PHST- 2004/11/13 09:00 [medline]
PHST- 2004/06/12 05:00 [entrez]
AID - 01101.2003 [pii]
AID - 10.1152/ajpheart.01101.2003 [doi]
PST - ppublish
SO  - Am J Physiol Heart Circ Physiol. 2004 Oct;287(4):H1452-8. doi: 
      10.1152/ajpheart.01101.2003. Epub 2004 Jun 10.