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Transactivation of the human interleukin-6 gene by human T-lymphotropic
virus type 1 Tax protein
I Yamashita, S Katamine, R Moriuchi, Y Nakamura, T Miyamoto, K Eguchi and S Nagataki
First Department of Internal Medicine, Nagasaki University School of
Medicine, Japan.
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.
Volume 84,
Issue 5,
pp. 1573-1578,
09/01/1994
Copyright © 1994 by The American Society of Hematology
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