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Human T cell leukemia virus type I tax enhances IL-4 gene expression in T cells

The human T cell leukemia virus type-1 (HTLV-1) is the etiologic agent of adult T cell leukemia (ATL). Since the HTLV-I-encoded transactivator Tax has been shown to activate many cellular genes including cytokine genes interleukin (IL-)1α , 2, 5, 6, 8, 10 and 15, we ask whether Tax also affects IL-4...

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Hauptverfasser: Li-Weber, Min (VerfasserIn) , Krammer, Peter H. (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 24 August 2001
In: European journal of immunology
Year: 2001, Jahrgang: 31, Heft: 9, Pages: 2623-2632
ISSN:1521-4141
DOI:10.1002/1521-4141(200109)31:9<2623::AID-IMMU2623>3.0.CO;2-4
Online-Zugang:Verlag, Volltext: https://doi.org/10.1002/1521-4141(200109)31:9<2623::AID-IMMU2623>3.0.CO;2-4
Verlag, Volltext: https://onlinelibrary.wiley.com/doi/abs/10.1002/1521-4141%28200109%2931%3A9%3C2623%3A%3AAID-IMMU2623%3E3.0.CO%3B2-4
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Verfasserangaben:Min Li‐Weber, Marco Giaisi, Katerina Chlichlia, Khashayarsha Khazaie and Peter H. Krammer

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520 |a The human T cell leukemia virus type-1 (HTLV-1) is the etiologic agent of adult T cell leukemia (ATL). Since the HTLV-I-encoded transactivator Tax has been shown to activate many cellular genes including cytokine genes interleukin (IL-)1α , 2, 5, 6, 8, 10 and 15, we ask whether Tax also affects IL-4 expression. In this study, we show that addition of recombinant Tax proteins greatly enhances IL-4 secretion in human peripheral primary T cells. Transient transfection studies showed that ectopic expression of Tax significantly enhanced IL-4 promoter activity. The IL-4 promoter contains a strong NF-IL6 (PRE-I element) and a NF-AT/NF-κB overlapping site (P1 element). We show that expression of Tax stimulates NF-IL6 binding to the PRE-I element and, consequently, enhancesPRE-I-mediated transcriptional activity. Using Jurkat T cell lines which stably express Tax fused to the hormone binding domain of the human estrogen receptor (ER), we show that Tax enhances endogenous IL-4 mRNA expression and increases IL-4 promoter activity in a hormone-dependent manner. Mutation analysis revealed that the IL-4 PRE-I (NF-IL6 site) and the P1 (NF-AT/NF-κB site) are involved in Tax-mediated transactivation. Our studies provide the first evidence of the functional involvement of Tax in IL-4 gene regulation. 
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