Linked Life Data

9916709

Source:http://linkedlifedata.com/resource/pubmed/id/9916709

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1999-2-8
pubmed:abstractText
The repetitive activation of T cells (priming) enhances the expression of many cytokines, such as IL-4, but not others, such as IL-2. Molecular mechanisms underlying selective expression of cytokines by T cells remain poorly understood. Here we show that priming of CD4 T cells selectively enhances IL-4 expression relative to IL-2 expression by a transcriptional mechanism involving nuclear factor of activated T cells (NFAT) proteins. As detected by in vivo footprinting, priming markedly increases the activation-dependent engagement of the P0 and P1 NFAT-binding elements of the IL-4 promoter. Moreover, each proximal P element is essential for optimal IL-4 promoter activity. Activated primed CD4 T cells contain more NFAT1 and support greater NFAT-directed transcription than unprimed CD4 T cells, while activator protein 1 binding and activator protein 1-mediated transcription by both cell types is similar. Increased expression of wild-type NFAT1 substantially increases IL-4 promoter activity in unprimed CD4 T cells, suggesting NFAT1 may be limiting for IL-4 gene expression in this cell type. Furthermore, a truncated form of NFAT1 acts as a dominant-negative, reducing IL-4 promoter activity in primed CD4 T cells and confirming the importance of endogenous NFAT to increased IL-4 gene expression by effector T cells. NFAT1 appears to be the major NFAT family member responsible for the initial increased expression of IL-4 by primed CD4 T cells.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
162
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
860-70
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:9916709-5' Untranslated Regions, pubmed-meshheading:9916709-Adult, pubmed-meshheading:9916709-Amino Acid Sequence, pubmed-meshheading:9916709-CD4-Positive T-Lymphocytes, pubmed-meshheading:9916709-Cell Nucleus, pubmed-meshheading:9916709-DNA-Binding Proteins, pubmed-meshheading:9916709-Gene Expression Regulation, pubmed-meshheading:9916709-Humans, pubmed-meshheading:9916709-Interleukin-4, pubmed-meshheading:9916709-Interphase, pubmed-meshheading:9916709-Lymphocyte Activation, pubmed-meshheading:9916709-Molecular Sequence Data, pubmed-meshheading:9916709-NFATC Transcription Factors, pubmed-meshheading:9916709-Nuclear Proteins, pubmed-meshheading:9916709-Promoter Regions, Genetic, pubmed-meshheading:9916709-Transcription, Genetic, pubmed-meshheading:9916709-Transcription Factors
pubmed:year
1999
pubmed:articleTitle
T cell priming enhances IL-4 gene expression by increasing nuclear factor of activated T cells.
pubmed:affiliation
Department of Pediatrics, University of Washington, Seattle 98195, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't