Transactivation of the human interleukin-6 gene by human T-lymphotropic virus type 1 Tax protein.
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.
Yamashita
I
I
First Department of Internal Medicine, Nagasaki University School of Medicine, Japan.
Katamine
S
S
Moriuchi
R
R
Nakamura
Y
Y
Miyamoto
T
T
Eguchi
K
K
Nagataki
S
S
D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000096:biosynthesis / Q000235:genetics; D002522:Chlorocebus aethiops; D017931:DNA Primers; D004742:Enhancer Elements, Genetic; D015870:Gene Expression; D016356:Gene Products, tax / Q000096:biosynthesis / Q000378:metabolism*; D015368:Human T-lymphotropic virus 1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis* / Q000235:genetics*; D007668:Kidney; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D015183:Restriction Mapping; D015533:Transcriptional Activation; D014162:Transfection; D014407:Tumor Cells, Cultured
D017931:DNA Primers; D016356:Gene Products, tax; D015850:Interleukin-6; D012333:RNA, Messenger; D015500:Chloramphenicol O-Acetyltransferase