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Transactivation of the human interleukin-6 gene by human T-lymphotropic virus type 1 Tax protein.
- Source :
-
Blood [Blood] 1994 Sep 01; Vol. 84 (5), pp. 1573-8. - Publication Year :
- 1994
-
Abstract
- Interleukin-6 (IL-6) is a multifunctional cytokine that regulates both humoral and cellular immune responses. Accumulating evidence suggests that the infection of T cells and other cell types with human T-lymphotropic virus type 1 (HTLV-1) results in the constitutive expression of IL-6. However, the underlying molecular mechanisms are little understood. When a reporter plasmid, pIL6-CAT-E3, in which the human IL-6 enhancer/promoter region from -630 to +14 was linked to the bacterial chloramphenicol acetyltransferase (CAT) gene, was transfected, HTLV-1-infected but not -uninfected T-cell lines activated the IL-6 promoter. This indicated the presence of a factor transactivating the IL-6 gene in the infected cells. To evaluate the involvement of the HTLV-1-encoded transacting factor (Tax) in this transactivation, we examined the effect of transient cotransfection with the Tax-expression plasmid, pMAX-Neo, on the transcription from the IL-6 promoter by use of COS1 cells. The cotransfected COS1 has about six-times greater the CAT activity than that transfected with pIL6-CAT-E3 alone. The analysis of a series of deletions of the IL-6 promoter suggested that the region (-105/-47) containing a NF kappa B site was crucial for the Tax responsiveness. We further examined the effect of Tax on endogenous IL-6 gene expression using the Jurkat clone, JPX-9, stably transfected with pMAX-Neo. JPX-9 accumulated steady state transcripts of the endogenous IL-6 gene in response to the induction of Tax expression. Our findings indicate an important role of the Tax protein in the expression of IL-6 in cells infected with HTLV-1.
- Subjects :
- Animals
Base Sequence
Cell Line
Chloramphenicol O-Acetyltransferase biosynthesis
Chloramphenicol O-Acetyltransferase genetics
Chlorocebus aethiops
DNA Primers
Enhancer Elements, Genetic
Gene Products, tax biosynthesis
Human T-lymphotropic virus 1 genetics
Humans
Kidney
Molecular Sequence Data
Polymerase Chain Reaction
Promoter Regions, Genetic
RNA, Messenger analysis
RNA, Messenger biosynthesis
Restriction Mapping
Transfection
Tumor Cells, Cultured
Gene Expression
Gene Products, tax metabolism
Human T-lymphotropic virus 1 physiology
Interleukin-6 biosynthesis
Interleukin-6 genetics
Transcriptional Activation
Subjects
Details
- Language :
- English
- ISSN :
- 0006-4971
- Volume :
- 84
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Blood
- Publication Type :
- Academic Journal
- Accession number :
- 8068947