Human T-cell leukemia virus type I tax transactivates the interleukin-6 gene in human rheumatoid synovial cells.
OBJECTIVE
To determine the effect of the human T cell leukemia virus type I (HTLV-I) tax gene on interleukin-6 (IL-6) production and gene transcription in synovial cells, we established the synovial cell line, E-11, from a patient with rheumatoid arthritis.


METHODS
E-11 cells were transfected with tax expression vector using the calcium phosphate coprecipitation method. IL-6 production and gene expression were investigated by ELISA and Northern blot analysis, respectively. To clarify how tax induces IL-6 gene expression, we used deletion analysis and chloramphenicol acetyltransferase (CAT) assay, and electrophoretic mobility shift assay (EMSA).


RESULTS
Transfection of the tax gene induced markedly high levels of IL-6 mRNA. Furthermore, the tax gene strongly transactivated IL-6 gene promoter activity assayed by CAT assay. By using deletion and site specific mutations, we have identified a nuclear factor (NF)-kappa B sequence (positions -73 to -63) which is essential for tax transaction. EMSA demonstrated the induction of specific binding of nuclear extracts to the NF-kappa B sequence by HTLV-I tax.


CONCLUSIONS
The HTLV-1 tax gene may transactivate IL-6 gene in the synovial cells through NF-kappa B and may contribute in the pathophysiology of HTLV-I associated arthritis.
Mori
N
N
First Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan.
Shirakawa
F
F
Abe
M
M
Kamo
Y
Y
Koyama
Y
Y
Murakami
S
S
Shimizu
H
H
Yamamoto
K
K
Oda
S
S
Eto
S
S
D001172:Arthritis, Rheumatoid / Q000235:genetics / Q000473:pathology / Q000821:virology*; D001483:Base Sequence; D002467:Cell Nucleus / Q000737:chemistry; D016355:Genes, pX / Q000502:physiology*; D015368:Human T-lymphotropic virus 1 / Q000235:genetics*; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics*; D015335:Molecular Probes / Q000235:genetics; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D011401:Promoter Regions, Genetic; D013583:Synovial Membrane / Q000473:pathology / Q000821:virology*; D014020:Tissue Extracts / Q000378:metabolism; D014158:Transcription, Genetic; D015533:Transcriptional Activation
D015850:Interleukin-6; D015335:Molecular Probes; D016328:NF-kappa B; D014020:Tissue Extracts