Cysteine-dependent immune regulation by TRX and MIF/GIF family proteins

Cysteine-dependent immune regulation by TRX and MIF/GIF family proteins
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DOI:
10.1016/j.imlet.2003.11.030
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发表时间:
2004-03-29
期刊:
影响因子:
4.4
通讯作者:
Yodoi, J
Yodoi, J
中科院分区:
医学3区
文献类型:
--
作者:
Kondo, N;Ishii, Y;Yodoi, J

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硫氧还蛋白(TRX)超家族蛋白,其含有保守的氧化还原活性位点-Cys-Xa. a. - Xa.a.- Cys-包括促炎细胞因子、巨噬细胞迁移抑制因子(MIF)和免疫调节细胞因子、糖基化抑制因子(GIF),其中Cys-60被半胱氨酸化。在本报告中,我们分析了TRX和MIF/GIF之间的功能相互作用。转染人TRX基因的稳定Jurkat T细胞系(TRX-转染子)对过氧化氢诱导的凋亡具有高度抵抗性,而转染载体的细胞系(模拟转染子)对过氧化氢诱导的凋亡没有抵抗性。转染TRX的细胞MIF/GIF蛋白表达水平低于假转染细胞。而来自MIF -/-小鼠的CD 4(+)-T细胞胞内TRX蛋白的表达水平显著高于来自背景BALB/c小鼠的CD 4(+)-T细胞。这些发现共同表明,氧化应激诱导的T淋巴细胞凋亡可能受到TRX和MIF/GIF表达的相互调节的保护。(C)2004 Elsevier B. V.保留所有权利。
Thioredoxin (TRX) superfamily proteins that contain a conserved redox-active site -Cys-Xa.a.-Xa.a.-Cys- includes proinflammatory cytokine, macrophage migration inhibiting factor (MIF) and the immune regulatory cytokine, glycosylation inhibiting factor (GIF) in which Cys-60 is cysteinylated. In this report, we have analyzed the functional interaction between TRX and MIF/GIF. The stable Jurkat T cell line transfected with human TRX gene (TRX-transfectant) was highly resistant to hydrogen peroxide-induced apoptosis, but not the cell line transfected with vector (mock-transfectant). The expression level of MIF/GIF protein of TRX-transfectant was lower than that of mock-transfectant. Conversely, the expression level of intracellular TRX protein in CD4(+)-T cells derived from MIF -/- mice were significantly higher than that from background BALB/c mice. These findings collectively suggest that oxidative stress-induced apoptosis on T lymphocytes might be protected by the reciprocal regulation of TRX and MIF/GIF expression. (C) 2004 Elsevier B.V. All rights reserved.