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-)1alpha, 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-kappaB 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-kappaB site) are involved in Tax-mediated transactivation. Our studies provide the first evidence of the functional involvement of Tax in IL-4 gene regulation.
journal_name
Eur J Immunoljournal_title
European journal of immunologyauthors
Li-Weber M,Giaisi M,Chlichlia K,Khazaie K,Krammer PHdoi
10.1002/1521-4141(200109)31:9<2623::aid-immu2623>3keywords:
subject
Has Abstractpub_date
2001-09-01 00:00:00pages
2623-32issue
9eissn
0014-2980issn
1521-4141pii
10.1002/1521-4141(200109)31:9<2623::AID-IMMU2623>3journal_volume
31pub_type
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