Source:http://linkedlifedata.com/resource/pubmed/id/15701058
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
6
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pubmed:dateCreated |
2005-5-17
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pubmed:abstractText |
Recent data have indicated that CRP (C-reactive protein) plays a role in atherosclerosis, in addition to being a marker for inflammatory diseases. IL-8 (interleukin-8), a CXC chemokine, is present in human coronary atheroma and promotes monocyte-endothelial cell adhesion. In the present study, we examined the effect of pitavastatin (NK-104), a synthetic statin (3-hydroxy-3-methylglutaryl CoA reductase inhibitor), on IL-8 production induced by CRP in human AoEC (aortic endothelial cells). We also investigated whether CRP can induce IL-8 production and if the activation of signalling pathways are functionally related. The concentrations of IL-8 in the media after stimulation with CRP were measured by ELISA, and the expression of IL-8 mRNA was assessed by Northern blot. The phosphorylation of MAPKs (mitogen-activated protein kinases) was determined by Western blot. The production of IL-8 induced by CRP (10 microg/ml) was enhanced significantly and was inhibited by pitavastatin. The expression of IL-8 mRNA was increased in a dose-dependent manner after stimulation with CRP (1-100 microg/ml), whereas expression of IL-8 mRNA induced by CRP (50 microg/ml) was significantly diminished by 5 microM pitavastatin. Furthermore, specific MAPK inhibitors (PD98059, SB203580 and SP600125) inhibited the expression of IL-8 mRNA induced by CRP (50 microg/ml). The phosphorylation of all three MAPKs [ERK (extracellular-signal-regulated kinase), p38 MAPK and JNK (c-Jun N-terminal kinase)] induced by CRP (10 microg/ml) was also significantly inhibited by pitavastatin. Our results suggest that CRP may play a role in atherosclerosis via IL-8 production and pitavastatin may prevent the progression of atherosclerosis not only by lowering plasma low-density lipoprotein cholesterol levels, but also by suppressing IL-8 production in endothelial cells through the inhibition of MAPK (ERK, p38 MAPK and JNK) pathways.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/C-Reactive Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Hydroxymethylglutaryl-CoA...,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-8,
http://linkedlifedata.com/resource/pubmed/chemical/Quinolines,
http://linkedlifedata.com/resource/pubmed/chemical/pitavastatin
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pubmed:status |
MEDLINE
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pubmed:month |
Jun
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pubmed:issn |
0143-5221
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
108
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
515-21
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:15701058-Analysis of Variance,
pubmed-meshheading:15701058-Aorta,
pubmed-meshheading:15701058-Arteriosclerosis,
pubmed-meshheading:15701058-Blotting, Northern,
pubmed-meshheading:15701058-Blotting, Western,
pubmed-meshheading:15701058-C-Reactive Protein,
pubmed-meshheading:15701058-Endothelial Cells,
pubmed-meshheading:15701058-Endothelium, Vascular,
pubmed-meshheading:15701058-Humans,
pubmed-meshheading:15701058-Hydroxymethylglutaryl-CoA Reductase Inhibitors,
pubmed-meshheading:15701058-Interleukin-8,
pubmed-meshheading:15701058-Quinolines
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pubmed:year |
2005
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pubmed:articleTitle |
Inhibitory effect of pitavastatin (NK-104) on the C-reactive-protein-induced interleukin-8 production in human aortic endothelial cells.
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pubmed:affiliation |
First Department of Internal Medicine, School of Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0194, Japan.
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pubmed:publicationType |
Journal Article
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