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

• Verfasst von: Li-Weber, Min [VerfasserIn]
• Verfasst von: Krammer, Peter H. [VerfasserIn]
• Titel: Human T cell leukemia virus type I tax enhances IL-4 gene expression in T cells
• Verf.angabe: Min Li‐Weber, Marco Giaisi, Katerina Chlichlia, Khashayarsha Khazaie and Peter H. Krammer
• E-Jahr: 2001
• Jahr: 24 August 2001
• Umfang: 10 S.
• Teil: volume:31
• Teil: year:2001
• Teil: number:9
• Teil: pages:2623-2632
• Teil: extent:10
• Fussnoten: Gesehen am 20.04.2021
• Titel Quelle: Enthalten in: European journal of immunology
• Ort Quelle: Weinheim : Wiley-VCH, 1971
• Jahr Quelle: 2001
• Band/Heft Quelle: 31(2001), 9, Seite 2623-2632
• ISSN Quelle: 1521-4141
• DOI: doi:10.1002/1521-4141(200109)31:9<2623::AID-IMMU2623>3.0.CO;2-4
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: CCAAT-enhancer binding protein
• Sach-SW: HTLV-1
• Sach-SW: IL-4
• Sach-SW: Tax
• K10plus-PPN: 1755488319

Abstract

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.