Linked Life Data

14630701

Source:http://linkedlifedata.com/resource/pubmed/id/14630701

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2004-1-13
pubmed:abstractText
E-selectin mediated cell-cell adhesion plays an important role in inflammatory processes and extravasation of tumor cells. Tumor necrosis factor-alpha (TNF-alpha) induces E-selectin gene and protein expression in primary human endothelial cells (HUVEC) and in an endothelial cell line (EA.hy-926). As shown by ELISA and FACS analyses, HMG-CoA reductase inhibitors (e.g., lovastatin) impair the TNF-alpha stimulated increase in E-selectin protein expression. Similar results were obtained for E-selectin mRNA expression and promoter activity, indicating that the effect of lovastatin is based on inhibition of gene expression. The effective inhibitory concentration of lovastatin was in a physiologically relevant range (IC50<0.1 microM). Lovastatin-mediated block of TNF-alpha induced E-selectin expression is due to inhibition of protein geranylgeranylation rather than farnesylation. Down-regulation of Rho signaling by coexpression of dominant-negative Rho mutants (i.e RhoA, RhoB and Rac) impaired TNF-alpha driven E-selectin gene expression, indicating Rho signaling to be essential for transcriptional activation of the E-selectin gene. Inhibition of E-selectin expression by lovastatin gives rise to a significant reduction in TNF-alpha stimulated adhesion of colon carcinoma cells to HUVEC. Furthermore, low concentration of lovastatin (i.e., < or =1 microM) attenuated TNF-alpha induced tumor cell invasion in vitro. The data support the view that statins might be clinically useful in protection against E-selectin mediated metastasis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1530-6860
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
18
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
140-2
pubmed:dateRevised
2005-11-17
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Lovastatin inhibits Rho-regulated expression of E-selectin by TNFalpha and attenuates tumor cell adhesion.
pubmed:affiliation
University of Mainz, Institute of Toxicology, Division of Applied Toxicology, Mainz, Germany.
pubmed:publicationType
Journal Article