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
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
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DOI：
10.1182/blood.v94.8.2862.420k24_2862_2870
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发表时间：
1999-10-15
期刊：
影响因子：
20.3
通讯作者：
Yamamoto, N
中科院分区：
文献类型：
--
作者：
Mori, N;Nunokawa, Y;Yamamoto, N
我们检测了人类诱导型一氧化氮合酶(HiNOS)基因的信使RNA(MRNAs)在一组人类T细胞系中的表达。逆转录聚合酶链式反应显示，人T细胞白血病病毒I型(HTLV-I)感染的T细胞株(MT-1、SLB-1和C5/MJ)表达hiNOS的mRNA，而TL-OM1或未感染的Jurkat、H9和CCRF-CEM不表达。MT-1、SLB-1和C5/MJ细胞感染HTLV-I后表达病毒反式激活因子Tax，而TL-OM1细胞虽然来源于成人T细胞白血病(ATL)白血病细胞，但不表达Tax。因此，Tax和hiNOS mRNA的表达之间存在相关性。Jurkat的hiNOS基因转录调控区被Tax激活，其中内源性的hiNOS是由Tax诱导的。缺失分析表明，包含核苷酸-159至-111的hiNOS区域含有最少的税务反应元件。在hiNOS启动子的-115位和-106位碱基上的NF-kappa B元件的突变仍然被TAX激活，而一个激活NF-KB途径有缺陷的TAX突变体保留了激活hiNOS启动子的能力。此外，I kappa Bα和I kappa Bβ显性负性突变体的过表达不能减少税收诱导的hiNOS基因的激活。此外，在ATL患者的白血病细胞中也检测到了hiNOS mRNA。我们的结果表明，hiNOS启动子包含一个位于-159和-111核苷酸之间的最小税务反应元件，这意味着hiNOS基因的表达参与了HTLV-I相关疾病的发病机制。(C)1999年由美国血液病学会主办。
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-kappa 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-KB pathway retained the ability to activate the hiNOS promoter. In addition, overexpression of the dominant-negative mutants of I kappa B alpha and I kappa B beta 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. (C) 1999 by The American Society of Hematology.