Elevated expression of CCL5/RANTES in adult T-cell leukemia cells: possible transactivation of the CCL5 gene by human T-cell leukemia virus type I tax.
HTLV-I is the etiologic agent of ATL and of tropical spastic paraparesis/HTLV-I-associated myelopathy. Infiltration of various tissues by circulating leukemic cells and HTLV-I-infected T cells is a characteristic of ATL and HTLV-I-associated inflammatory diseases. Chemokines play important roles in migration and tissue localization of various lymphocyte subsets. Here, we report the highly frequent expression of CCL5 (RANTES) in ATL and HTLV-I-infected T-cell lines. Among various human T-cell lines, those infected with HTLV-I selectively expressed the CCL5 gene and secreted CCL5. Furthermore, CCL5 was expressed by leukemic cells in peripheral blood and lymph nodes from patients with ATL. Inducible expression of HTLV-I transcriptional activator Tax in a human T-cell line Jurkat, up-regulated CCL5 mRNA and induced CCL5 secretion. Analysis of the CCL5 promoter revealed that this gene is activated by Tax, via the activation of NF-kappaB, whose responsive element, R(A/B), is located at positions -71 to -43 relative to the putative transcription start site. Aberrant expression of CCL5 by HTLV-I-infected T cells may impact on the pathophysiology of HTLV-I-associated diseases.
Mori
Naoki
N
Division of Molecular Virology and Oncology, Graduate School of Medicine, University of the Ryukyus, Nishihara, Japan. n-mori@med.u-ryukyu.ac.jp
Krensky
Alan M
AM
Ohshima
Koichi
K
Tomita
Mariko
M
Matsuda
Takehiro
T
Ohta
Takao
T
Yamada
Yasuaki
Y
Tomonaga
Masao
M
Ikeda
Shuichi
S
Yamamoto
Naoki
N
D002460:Cell Line; D018946:Chemokine CCL5; D019742:Chemokines, CC / Q000096:biosynthesis* / Q000235:genetics*; D016355:Genes, pX; D015368:Human T-lymphotropic virus 1 / Q000472:pathogenicity*; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000235:genetics* / Q000821:virology*; D011401:Promoter Regions, Genetic; D012313:RNA / Q000096:biosynthesis; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
C483024:CCL5 protein, human; D018946:Chemokine CCL5; D019742:Chemokines, CC; D012313:RNA