Linked Life Data

15191888

Source:http://linkedlifedata.com/resource/pubmed/id/15191888

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2004-9-16
pubmed:abstractText
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0363-6135
pubmed:author
pubmed:issnType
Print
pubmed:volume
287
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
H1452-8
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:15191888-Antineoplastic Agents, pubmed-meshheading:15191888-Aorta, pubmed-meshheading:15191888-Arteriosclerosis, pubmed-meshheading:15191888-Cells, Cultured, pubmed-meshheading:15191888-Chemokine CCL2, pubmed-meshheading:15191888-Endothelium, Vascular, pubmed-meshheading:15191888-Humans, pubmed-meshheading:15191888-Mitogen-Activated Protein Kinases, pubmed-meshheading:15191888-NF-kappa B, pubmed-meshheading:15191888-Phosphotransferases (Alcohol Group Acceptor), pubmed-meshheading:15191888-Promoter Regions, Genetic, pubmed-meshheading:15191888-RNA, Messenger, pubmed-meshheading:15191888-RNA, Small Interfering, pubmed-meshheading:15191888-Signal Transduction, pubmed-meshheading:15191888-Stress, Mechanical, pubmed-meshheading:15191888-Tumor Necrosis Factor-alpha, pubmed-meshheading:15191888-Up-Regulation, pubmed-meshheading:15191888-p38 Mitogen-Activated Protein Kinases
pubmed:year
2004
pubmed:articleTitle
Sphingosine kinase-1 mediates TNF-alpha-induced MCP-1 gene expression in endothelial cells: upregulation by oscillatory flow.
pubmed:affiliation
Discovery Research, AtheroGenics, Inc., 8995 Westside Parkway, Alpharetta, GA 30004, USA. xchen@atherogenics.com
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't