Linked Life Data

10954918

Source:http://linkedlifedata.com/resource/pubmed/id/10954918

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
8
pubmed:dateCreated
2001-2-2
pubmed:abstractText
To delineate the functional role of the tumor necrosis factor-alpha (TNF-alpha) activator protein-1 (AP-1)/cAMP-responsive element (CRE)-like binding element (TAC), we transfected the TNF-alpha promoter lacking TAC into THP-1 monocytic cells and stimulated with lipopolysaccharide (LPS). Chloramphenicol acetyltransferase (CAT) activity was reduced by 22-fold, suggesting that TAC plays a role in LPS induction of the TNF-alpha promoter. Exposure to LPS resulted in the maximum release of soluble TNF-alpha by 2 h. Electrophoretic mobility shift assays (EMSA) using the TAC element as a probe showed a unique pattern for LPS-activated cells: the disappearance of the upper band of a doublet seen in untreated and all-trans retinoic acid (ATRA)-treated cells. Supershift analysis identified c-Jun and activating transcription factor-2 (ATF-2) as components of the LPS-stimulated binding complex. Jun N-terminal kinase (JNK), a known phosphorylator of c-Jun and ATF-2, increased in activity in LPS-stimulated monocytes. ATRA, on the contrary, did not activate JNK activity up to 72 h. Nuclear extracts from LPS-stimulated cells showed an increase in phosphorylated c-Jun by immunoblotting. Likewise, phosphorylated c-Jun bound to the TAC element, suggesting that c-Jun is activated by JNK to transactivate the TNF-alpha promoter in LPS-treated monocytes. Thus, phosphorylated c-Jun and ATF-2 play a role in activating the TAC element of the TNF-alpha promoter.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1079-9907
pubmed:author
pubmed:issnType
Print
pubmed:volume
20
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
741-8
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2000
pubmed:articleTitle
A distinct element involved in lipopolysaccharide activation of the tumor necrosis factor-alpha promoter in monocytes.
pubmed:affiliation
Department of Bioimmunotherapy, The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't