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Blood, Vol. 94 No. 8 (October 15), 1999:
pp. 2862-2870
Expression of Human Inducible Nitric Oxide Synthase Gene in T-Cell
Lines Infected With Human T-Cell Leukemia Virus Type-I and Primary
Adult T-Cell Leukemia Cells
Naoki Mori,
Youichi Nunokawa,
Yasuaki Yamada,
Shuichi Ikeda,
Masao Tomonaga, and
Naoki Yamamoto
From the Department of Preventive Medicine and AIDS Research,
Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan;
the Department of Laboratory Medicine, Nagasaki University School of
Medicine, Nagasaki, Japan; the Department of Hematology, Atomic Disease
Institute, Nagasaki University School of Medicine, Nagasaki, Japan;
City of Sasebo General Hospital, Sasebo, Japan; and Suntory Institute
for Biomedical Research, Osaka, Japan.
We examined the expression of messenger RNA (mRNA) of the human
inducible nitric oxide synthase (hiNOS) gene in a panel of human T-cell lines. Reverse transcriptase-polymerase chain reaction showed that human T-cell leukemia virus type-I (HTLV-I)-infected T-cell lines (MT-1, SLB-1, and C5/MJ) expressed mRNA for the hiNOS, but
TL-Om1 or uninfected Jurkat, H9, and CCRF-CEM did not. The MT-1, SLB-1,
and C5/MJ cell lines are infected with HTLV-I and express the viral
transactivator Tax, whereas TL-Om1 cells, although derived from adult
T-cell leukemia (ATL) leukemic cells, do not express Tax. There was,
thus, a correlation between Tax and hiNOS mRNA expression. The
transcriptional regulatory region of the hiNOS gene was
activated by Tax in Jurkat, in which endogenous hiNOS is induced by
Tax. Deletion analysis showed that the region of hiNOS encompassing
nucleotides  159 to 111 contained the minimum Tax-responsive
elements. Mutations in the NF- B element at position 115 and
106 bp in the hiNOS promoter were still activated by Tax, and a Tax
mutant defective for activation of the NF-B pathway retained the
ability to activate the hiNOS promoter. In addition, overexpression of
the dominant-negative mutants of IB and I B failed to
reduce Tax-induced activation of hiNOS gene. Furthermore, hiNOS
mRNA was detected in leukemic cells from ATL patients. Our results show
that the hiNOS promoter contains a minimum Tax-responsive element
located between nucleotides 159 and 111, and imply that the
expression of the hiNOS gene is involved in the pathogenesis of
HTLV-I-associated diseases.
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