Human T cell leukemia virus type-I Tax activates human macrophage inflammatory protein-3 alpha/CCL20 gene transcription via the NF-kappa B pathway.
Infection by human T cell leukemia virus type (HTLV)-I is associated with several diseases, including adult T cell leukemia and HTLV-I-associated myelopathy/tropical spastic paraparesis. Leukocytes are attracted to the sites of inflammation by chemotactic factors. Macrophage inflammatory protein (MIP)-3 alpha/CCL20 is a recently isolated member of the CC subfamily of chemokines and has been proposed as a crucial factor to elicit inflammatory reactions. We now report that endogenous MIP-3 alpha mRNA levels are elevated in HTLV-I-infected T cell lines and in a human T cell line following the induced expression of the HTLV-I-encoded transactivator, Tax. Analysis of the human MIP-3 alpha promoter revealed that this gene is activated by Tax, via the activation of nuclear factor (NF)-kappa B, whose responsive element, -82-kappa B, is located at a position between -82 and -91 relative to the putative transcription start site. With an electromobility shift assay we further demonstrated that the -82-kappa B element was bound by the Tax-activated p50/p65 heterodimers of NF-kappa B. Expression of the specific receptor of MIP-3 alpha, CCR6, was also increased in HTLV-I-infected T cell lines, suggesting an autocrine and/or paracrine mechanism to establish the pathogenesis of HTLV-I-associated diseases.
Imaizumi
Yoshitaka
Y
Division of Cytokine Signaling, Department of Molecular Microbiology and Immunology, Nagasaki University Graduate School of Medical Sciences, Nagasaki 852-8523, Japan.
Sugita
Shinichi
S
Yamamoto
Kazuo
K
Imanishi
Daisuke
D
Kohno
Tomoko
T
Tomonaga
Masao
M
Matsuyama
Toshifumi
T
D054418:Chemokine CCL20; D019742:Chemokines, CC / Q000235:genetics*; D015696:Gene Products, tat / Q000502:physiology*; D015368:Human T-lymphotropic virus 1 / Q000502:physiology*; D006801:Humans; D019169:Jurkat Cells; D019402:Macrophage Inflammatory Proteins / Q000235:genetics*; D016328:NF-kappa B / Q000502:physiology*; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000032:analysis; D054399:Receptors, CCR6; D019707:Receptors, Chemokine / Q000032:analysis; D014158:Transcription, Genetic
C108355:CCL20 protein, human; C106311:CCR6 protein, human; D054418:Chemokine CCL20; D019742:Chemokines, CC; D015696:Gene Products, tat; D019402:Macrophage Inflammatory Proteins; D016328:NF-kappa B; D012333:RNA, Messenger; D054399:Receptors, CCR6; D019707:Receptors, Chemokine