Production of interleukin 8 in adult T-cell leukemia cells: possible transactivation of the interleukin 8 gene by human T-cell leukemia virus type I tax.
Interleukin 8 (IL-8) mRNA was detected in peripheral leukemic cells obtained from adult T-cell leukemia patients, as well as in cultured human T-cell leukemia virus type I (HTLV-I)-infected T-cell lines (HUT-102, MT-1, SALT-3, and SKT-1B). With the use of ELISA, IL-8 protein was also detected in the culture medium of these cells and in the extracellular fluids of patients. Furthermore, we demonstrated that the HTLV-I-derived transactivator protein, tax, could stimulate endogenous IL-8 gene expression in an uninfected T-cell line (Jurkat) and in a rheumatoid synovial cell line (E-11). Induction of IL-8 by tax at protein level was also demonstrated in transfected cells. We found that the IL-8 NF-kappa B-binding site specifically formed a complex with NF-kappa B-containing nuclear extracts from HTLV-I-infected T-cell lines and freshly isolated leukemic cells from adult T-cell leukemia patients. Finally, transfection of HTLV-I tax into Jurkat cells resulted in induction of specific binding of nuclear extracts to the NF-kappa B sequence. These results suggest that the HTLV-I tax gene may transactivate the IL-8 gene through the kappa B site in HTLV-I-infected cells and that constitutive expression of the IL-8 gene may play a role in HTLV-I-associated pathogenesis.
Mori
N
N
First Department of Internal Medicine, University of Occupational and Environmental Health, School of Medicine, Kitakyushu, Japan.
Murakami
S
S
Oda
S
S
Prager
D
D
Eto
S
S
D000208:Acute Disease; D001483:Base Sequence; D017931:DNA Primers / Q000737:chemistry; D015972:Gene Expression Regulation, Neoplastic; D016355:Genes, pX; D015368:Human T-lymphotropic virus 1 / Q000235:genetics*; D006801:Humans; D066298:In Vitro Techniques; D016209:Interleukin-8 / Q000096:biosynthesis* / Q000235:genetics; D015458:Leukemia, T-Cell / Q000378:metabolism*; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D014407:Tumor Cells, Cultured
D017931:DNA Primers; D016209:Interleukin-8; D016328:NF-kappa B; D009687:Nuclear Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm