Induction of ICAM-1 and LFA-3 by Tax1 of human T-cell leukemia virus type 1 and mechanism of down-regulation of ICAM-1 or LFA-1 in adult-T-cell-leukemia cell lines.
The present study was undertaken to determine the role of HTLV-I TaxI in the up-regulation of ICAM-I and LFA-3 in human T cells transformed with HTLV-I and the mechanism of down-regulation of ICAM-I and LFA-I in ATL-derived cell lines. Induction of TaxI in a human T-cell line Jurkat carrying the TaxI gene under the metallothionein promoter led to increases in mRNA and surface expression of ICAM-I. The response of LFA-3 to TaxI induction was, on the other hand, relatively slow and weak, and might be indirect. Transactivation of the ICAM-I promoter by TaxI was further shown by co-transfection of a CAT reporter construct with the ICAM-I promoter and a plasmid expressing TaxI. The mechanism of down-regulation of ICAM-I or LFA-I in 4 ATL cell lines was next examined. ICAM-I mRNA was quite low in MT-I, but no genomic changes were found. The CAT reporter with the ICAM-I promoter was inactive in MT-I. Finally, combined treatment of MT-I with 5-azacytidine and IFN-gamma induced re-expression of ICAM-I. Collectively, (a) transcriptional factor(s) necessary for expression of ICAM-I gene may be repressed in MT-I through DNA methylation. Three other ATL cell lines (TL-OmI, H582, HuT102) were found to have little mRNA for the LFA-I beta chain (CD18). H582 and HuT102 were also negative for the LFA-I alpha chain (CDIIa) mRNA. No genomic changes were found, and a CAT reporter gene with the CD18 promoter was inactive in the 3 of them, again suggesting lack of (a) transcriptional factor(s) necessary for CD18 expression.
Tanaka
Y
Y
Shionogi Institute for Medical Science, Osaka, Japan.
Fukudome
K
K
Hayashi
M
M
Takagi
S
S
Yoshie
O
O
D015703:Antigens, CD / Q000096:biosynthesis; D001483:Base Sequence; D015152:Blotting, Northern; D015139:Blotting, Southern; D018968:CD58 Antigens; D015815:Cell Adhesion Molecules / Q000096:biosynthesis* / Q000235:genetics; D002461:Cell Line, Transformed / Q000378:metabolism; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D017931:DNA Primers; D004279:DNA, Viral / Q000235:genetics; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D015967:Gene Expression Regulation, Viral; D016356:Gene Products, tax / Q000378:metabolism; D017930:Genes, Reporter; D015756:Genes, tat / Q000502:physiology*; D015368:Human T-lymphotropic virus 1 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000096:biosynthesis; D015458:Leukemia, T-Cell / Q000378:metabolism / Q000821:virology*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000096:biosynthesis; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D008745:Methylation; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D012097:Repressor Proteins / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism* / Q000821:virology; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured / Q000378:metabolism; D015854:Up-Regulation
D015703:Antigens, CD; D018968:CD58 Antigens; D015815:Cell Adhesion Molecules; D017931:DNA Primers; D004279:DNA, Viral; D016356:Gene Products, tax; D016169:Lymphocyte Function-Associated Antigen-1; D008562:Membrane Glycoproteins; D012097:Repressor Proteins; D018799:Intercellular Adhesion Molecule-1; D015500:Chloramphenicol O-Acetyltransferase