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

Min Li-Weber, Marco Giaisi, Katerina Chlichlia, Khashayarsha Khazaie, Peter H. Krammer

Research output: Contribution to journalArticle

14 Citations (Scopus)

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, enhances PRE-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.

Original languageEnglish (US)
Pages (from-to)2623-2632
Number of pages10
JournalEuropean Journal of Immunology
Volume31
Issue number9
DOIs
StatePublished - 2001
Externally publishedYes

Fingerprint

Human T-lymphotropic virus 1
Interleukin-4
T-Lymphocytes
Gene Expression
CCAAT-Enhancer-Binding Protein-beta
tax Gene Products
Hormones
Genes
Deltaretrovirus
Adult T Cell Leukemia Lymphoma
Jurkat Cells
Trans-Activators
Interleukin-1
Recombinant Proteins
Estrogen Receptors
Transcriptional Activation
Interleukin-2
Transfection
Cytokines
Cell Line

Keywords

  • CCAAT-enhancer binding protein
  • HTLV-1
  • IL-4
  • Tax

ASJC Scopus subject areas

  • Immunology

Cite this

Human T cell leukemia virus type I tax enhances IL-4 gene expression in T cells. / Li-Weber, Min; Giaisi, Marco; Chlichlia, Katerina; Khazaie, Khashayarsha; Krammer, Peter H.

In: European Journal of Immunology, Vol. 31, No. 9, 2001, p. 2623-2632.

Research output: Contribution to journalArticle

Li-Weber, Min ; Giaisi, Marco ; Chlichlia, Katerina ; Khazaie, Khashayarsha ; Krammer, Peter H. / Human T cell leukemia virus type I tax enhances IL-4 gene expression in T cells. In: European Journal of Immunology. 2001 ; Vol. 31, No. 9. pp. 2623-2632.
@article{d59c2ac748b44afaa4f092b8f8b45bc5,
title = "Human T cell leukemia virus type I tax enhances IL-4 gene expression in T cells",
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, enhances PRE-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.",
keywords = "CCAAT-enhancer binding protein, HTLV-1, IL-4, Tax",
author = "Min Li-Weber and Marco Giaisi and Katerina Chlichlia and Khashayarsha Khazaie and Krammer, {Peter H.}",
year = "2001",
doi = "10.1002/1521-4141(200109)31:9<2623::AID-IMMU2623>3.0.CO;2-4",
language = "English (US)",
volume = "31",
pages = "2623--2632",
journal = "European Journal of Immunology",
issn = "0014-2980",
publisher = "Wiley-VCH Verlag",
number = "9",

}

TY - JOUR

T1 - Human T cell leukemia virus type I tax enhances IL-4 gene expression in T cells

AU - Li-Weber, Min

AU - Giaisi, Marco

AU - Chlichlia, Katerina

AU - Khazaie, Khashayarsha

AU - Krammer, Peter H.

PY - 2001

Y1 - 2001

N2 - 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, enhances PRE-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.

AB - 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, enhances PRE-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.

KW - CCAAT-enhancer binding protein

KW - HTLV-1

KW - IL-4

KW - Tax

UR - http://www.scopus.com/inward/record.url?scp=0034806874&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034806874&partnerID=8YFLogxK

U2 - 10.1002/1521-4141(200109)31:9<2623::AID-IMMU2623>3.0.CO;2-4

DO - 10.1002/1521-4141(200109)31:9<2623::AID-IMMU2623>3.0.CO;2-4

M3 - Article

C2 - 11536160

AN - SCOPUS:0034806874

VL - 31

SP - 2623

EP - 2632

JO - European Journal of Immunology

JF - European Journal of Immunology

SN - 0014-2980

IS - 9

ER -