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

Citation
M. Li-weber et al., Human T cell leukemia virus type I Tax enhances IL-4 gene expression in T cells, EUR J IMMUN, 31(9), 2001, pp. 2623-2632
Citations number
62
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Immunology
Journal title
EUROPEAN JOURNAL OF IMMUNOLOGY
ISSN journal
0014-2980 → ACNP
Volume
31
Issue
9
Year of publication
2001
Pages
2623 - 2632
Database
ISI
SICI code
0014-2980(200109)31:9<2623:HTCLVT>2.0.ZU;2-M
Abstract
The human T cell leukemia virus type-1 (HTLV-1) is the etiologic agent of a dult T cell leukemia (ATL). Since the HTLV-I-encoded transactivator Tax has been shown to activate many cellular genes including cytokine genes interl eukin (IL-)1 alpha, 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 pr oteins greatly enhances IL-4 secretion in human peripheral primary T cells. Transient transfection studies showed that ectopic expression of Tax signi ficantly enhanced IL-4 promoter activity. The IL-4 promoter contains a stro ng NF-IL6 (PRE-I element) and a NF-AT/NF-kappaB overlapping site (P1 elemen t). We show that expression of Tax stimulates NF-IL6 binding to the PRE-I e lement and, consequently, enhances PRE-I-mediated transcriptional activity. Using Jurkat T cell lines which stably express Tax fused to the hormone bi nding 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 (N F-IL6 site) and the P1 (NF-AT/NF-kappaB site) are involved in Tax-mediated transactivation. Our studies provide the first evidence of the functional i nvolvement of Tax in IL-4 gene regulation.