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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1999-8-16
pubmed:abstractText
Vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) are upregulated in vascular endothelial and smooth muscle cells by cytokines produced at sites of inflammation. The cytokine profile for induction of VCAM-1, however, is different for the two cell types. Tumor necrosis factor-alpha (TNF-alpha) induced both VCAM-1 and ICAM-1 expression in human umbilical vein endothelial cells (HUVECs; ED50 approximately 300 and 30 U/ml, respectively). TNF-alpha and interleukin-1beta (IL-1beta) stimulated cell surface ICAM-1 expression, but not VCAM-1 expression, in human aortic smooth muscle cells (HASMCs). Conversely, IL-4 was a potent VCAM-1 inducer in HASMCs (ED50 approximately 100 pg/ml) but did not induce ICAM-1 expression. Nuclear extracts from IL-4-treated cells were compared with untreated cells for relative nuclear factor-kappa B (NF-kappaB) levels by using an electrophoretic mobility shift assay and surface plasmon resonance techniques. No significant increase in nuclear NF-kappaB DNA binding activity was detected in IL-4-treated HASMCs by either method of analysis. IL-1beta and TNF-alpha stimulated nuclear NF-kappaB levels by about fourfold and fivefold, respectively, in HASMCs. The antioxidant pyrrolidine dithiocarbamate (PDTC) similarly inhibited VCAM-1 upregulation in HASMCs incubated with IL-4 and in HUVECs incubated with TNF-alpha (IC50s of 25 and 40 microM, respectively). These data suggest that a significant increase in nuclear NF-kappaB levels is not necessary or sufficient for VCAM-1 upregulation in HASMCs and does not determine the relative sensitivity to inhibition of gene expression by PDTC.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0021-9541
pubmed:author
pubmed:issnType
Print
pubmed:volume
180
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
381-9
pubmed:dateRevised
2004-11-17
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Induction of vascular cell adhesion molecule-1 expression by IL-4 in human aortic smooth muscle cells is not associated with increased nuclear NF-kappaB levels.
pubmed:affiliation
Hoechst Marion Roussel, Inc., Bridgewater, New Jersey 08807-0800, USA. paul.wright@hmrag.com
pubmed:publicationType
Journal Article