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Predicate | Object |
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rdf:type | |
lifeskim:mentions |
umls-concept:C0021756,
umls-concept:C0030943,
umls-concept:C0040648,
umls-concept:C0040649,
umls-concept:C0080202,
umls-concept:C0205263,
umls-concept:C0242633,
umls-concept:C0441712,
umls-concept:C0443199,
umls-concept:C0591833,
umls-concept:C0851285,
umls-concept:C1157563,
umls-concept:C1423842,
umls-concept:C2249859,
umls-concept:C2362651
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pubmed:issue |
3
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pubmed:dateCreated |
1994-3-9
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pubmed:abstractText |
Regulation of IL-2 gene expression in response to receptor-mediated stimuli is known to be mediated primarily by the IL-2 transcriptional enhancer and multiple transcription factors. However, the mechanism that controls the differential expression of the IL-2 gene in both human and murine CD4+ Th cell subsets (Th1-IL-2+ and Th2-IL-2-) is not clearly understood. Differential IL-2 gene expression was assessed in murine Th1 and Th2 subsets by analyzing the expression of a Escherichia coli lacZ reporter gene under control of the human IL-2 enhancer (IL2ZH) transfected in both T cell subsets. Stimulation of transfected T cells with the mitogen Con A, anti-CD3 Ab, or PMA plus ionomycin activated the IL2ZH construct in Th1 but not Th2 cells. However, IL2ZH was activated in stimulated Th2 cells that were co-transfected with a vector that overexpressed the eukaryotic initiation factor 4E (eIF-4E). It has been shown that eIF-4E is rate limiting for protein synthesis and its overexpression leads to increased rates of protein synthesis. Hence, eIF-4E overexpression could have overcome a deficiency in transcriptionally active levels of IL-2 regulatory factors in Th2 cells leading to IL-2 enhancer activation. This possibility was supported by demonstrating that transcriptionally active levels of the critical IL-2 transcription factor, nuclear factor of activated T cells (NF-AT), occurred only in Th2 cells overexpressing eIF-4E but not in normal Th2 cells, thus indicating that the inability of Th2 cells to express IL-2 was associated with inadequate levels of at least one transcription factor, NF-AT. Moreover, these results were confirmed by the observation that eIF-4E overexpression augmented NF-AT binding activity in Th2 cells. These data suggest that concentrations of inducible transcription factors are a major component of the regulatory mechanisms dictating IL-2 expression and may be under translational control in Th1/Th2 T cell subsets.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Eukaryotic Initiation Factor-4E,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-2,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide Initiation Factors,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0022-1767
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
152
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1171-81
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:7905499-Animals,
pubmed-meshheading:7905499-CD4-Positive T-Lymphocytes,
pubmed-meshheading:7905499-Enhancer Elements, Genetic,
pubmed-meshheading:7905499-Eukaryotic Initiation Factor-4E,
pubmed-meshheading:7905499-Gene Expression Regulation,
pubmed-meshheading:7905499-Interleukin-2,
pubmed-meshheading:7905499-Mice,
pubmed-meshheading:7905499-Mice, Inbred C57BL,
pubmed-meshheading:7905499-Peptide Initiation Factors,
pubmed-meshheading:7905499-Protein Biosynthesis,
pubmed-meshheading:7905499-RNA, Messenger,
pubmed-meshheading:7905499-T-Lymphocyte Subsets,
pubmed-meshheading:7905499-T-Lymphocytes, Helper-Inducer,
pubmed-meshheading:7905499-Transcription, Genetic,
pubmed-meshheading:7905499-Transcription Factors
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pubmed:year |
1994
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pubmed:articleTitle |
Mechanism of differential regulation of IL-2 in murine Th1 and Th2 T cell subsets. 1. Induction of IL-2 transcription in Th2 cells by up-regulation of transcription factors with the protein synthesis initiation factor 4E.
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pubmed:affiliation |
Department of Microbiology and Immunology, University of Kentucky College of Medicine, Lexington 40536.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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