Linked Life Data

12099998

Source:http://linkedlifedata.com/resource/pubmed/id/12099998

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2002-7-8
pubmed:abstractText
1. Inhibitors of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase (statins) reduce serum cholesterol and have proven benefits in the treatment of cardiovascular disease. However, recent work suggests that statins may exert immunosuppressive effects in isolated lymphocytes and in solid organ transplant recipients. Fluvastatin does not interfere with the metabolism of commonly used immunosuppressive agents and, therefore, may have benefits in transplant recipients. 2. The aim of the present study was to investigate the potential immunomodulatory effects of fluvastatin in vitro in human lymphocytes and the underlying effects on signal transduction. 3. In vitro, fluvastatin (10 micromol/L) caused a time-dependent inhibition of T cell proliferation in response to cross-linking of CD3. 4. Thymidine incorporation was reduced by 22, 81 and 92% at days 1, 3 and 5, respectively. 5. Mevalonate (1 micromol/L) treatment for 4 or 24 h significantly reduced the inhibitory effects of fluvastatin; the reversal was abrogated by simultaneous exposure to mevalonate and a farnesyl transferase inhibitor. 6. At a subcellular level, fluvastatin treatment was associated with reduced functional activity of Ras-dependent extracellular signal-regulated kinase pathways and of Rho-dependent p38 activation. 7. These data suggest that the potential immunosuppressive actions of statins involve inhibition of subcellular pathways dependent on isoprenylation of signal peptides, including Ras, Rho and related G-proteins.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0305-1870
pubmed:author
pubmed:issnType
Print
pubmed:volume
29
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
673-8
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Inhibition of proliferation and signalling mechanisms in human lymphocytes by fluvastatin.
pubmed:affiliation
Department of Medicine and Therapeutics, University of Glasgow, Western Infirmary, Glasgow, UK.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't