Linked Life Data

11886526

Source:http://linkedlifedata.com/resource/pubmed/id/11886526

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2002-3-11
pubmed:abstractText
Epidermal keratinocyte-derived overexpression of vascular endothelial growth factor has been functionally linked to increased density of tortuous and hyperpermeable dermal microvessels, representing a characteristic component of cutaneous inflammation. We hypothesized that potent anti-inflammatory properties of synthetic glucocorticoids are attributed in part to their interference with the regulated vascular endothelial growth factor expression by keratinocytes. As vascular endothelial growth factor is markedly upregulated by autocrine transforming growth factor alpha and paracrine hepatocyte growth factor/scatter factor expression, the effect of glucocorticoids on growth-factor-induced vascular endothelial growth factor production by primary and immortalized keratinocytes was examined. Glucocorticoids were shown to suppress vascular endothelial growth factor protein and mRNA expression in a concentration- and time-dependent fashion. In transcriptional activation studies, however, common 5'-regulatory regions of the vascular endothelial growth factor gene failed to confer inhibitory glucocorticoid effects. Instead, glucocorticoids were shown to increase vascular endothelial growth factor mRNA turnover, indicating that post-transcriptional modes of glucocorticoid action are employed to negatively regulate induced vascular endothelial growth factor expression. Together, these studies identify vascular endothelial growth factor upregulation by epidermal keratinocytes as a putative target of glucocorticoid action in cutaneous inflammation. Our data provide strong evidence that mRNA destabilization may represent a mechanism by which glucocorticoids inhibit growth-factor-regulated vascular endothelial growth factor gene expression by keratinocytes.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0022-202X
pubmed:author
pubmed:issnType
Print
pubmed:volume
117
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1581-7
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
Decreased mRNA stability as a mechanism of glucocorticoid-mediated inhibition of vascular endothelial growth factor gene expression by cultured keratinocytes.
pubmed:affiliation
Zentrum der Dermatologie, Klinikum der J. W. Goethe-Universität, Frankfurt am Main, Germany. Gille@em.uni-frankfurt.de
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't