Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
1995-5-15
pubmed:abstractText
Glucocorticosteroids have a wide variety of effects which result in the long-term dampening of inflammatory responses. An important site of steroid action may be on the control of the activator protein-1 (AP-1) binding to deoxyribonucleic acid (DNA). AP-1 is a proinflammatory transcription factor composed of a heterodimer of Fos and Jun proto-oncogenes, which can be induced by phorbol esters and various cytokines. We have examined the hypothesis that dexamethasone may inhibit inflammation via an effect on AP-1 activation in human lung tissue. The effect of dexamethasone on the phorbol ester and cytokine activation of AP-1 and its monomers was examined in human lung tissue obtained from transplantation donors. AP-1 activation was measured by its ability to bind DNA, its localization in the nucleus by Western blotting, and the levels of fos and jun messenger ribonucleic acids (mRNAs) using Northern blotting. The phorbol ester, phorbol myristate acetate (PMA), caused a significant 2-3 fold increase in AP-1 DNA binding, which was sustained for 24 h and completely attenuated by co-incubation with dexamethasone. Dexamethasone alone caused a 40% decrease in AP-1 DNA binding. Dexamethasone modulated the expression of both c-jun and c-fos mRNA and produced long-term (24 h) 40% reduction in both mRNAs when compared to control tissues. PMA induced a rapid and prolonged increase in c-Fos and c-Jun nuclear localization, which was not attenuated by co-incubation with dexamethasone.(ABSTRACT TRUNCATED AT 250 WORDS)
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0903-1936
pubmed:author
pubmed:issnType
Print
pubmed:volume
7
pubmed:geneSymbol
c-fos, c-jun
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2117-23
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
1994
pubmed:articleTitle
Effects of dexamethasone on cytokine and phorbol ester stimulated c-Fos and c-Jun DNA binding and gene expression in human lung.
pubmed:affiliation
Dept of Thoracic Medicine, National Heart and Lung Institute, London, UK.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't