Vitamin K3 suppressed inflammatory and immune responses in a redox-dependent manner
Vitamin K3 suppressed inflammatory and immune responses in a redox-dependent manner
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DOI：
10.3109/10715762.2011.585647
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发表时间：
2011-08-01
影响因子：
3.3
通讯作者：
Sainis, Krishna B.
中科院分区：
文献类型：
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作者：
Checker, Rahul;Sharma, Deepak;Sainis, Krishna B.
最近的研究表明，细胞氧化还原状态可能在几种免疫功能的调节中起关键作用。用维生素K3（美萘醌）治疗淋巴细胞导致细胞GSH/GSSG比值显著降低，同时ROS水平升高。在体外实验中，它还抑制了cona诱导的淋巴细胞和CD4+T细胞的增殖和细胞因子的产生。甲萘醌的免疫抑制作用仅被含硫醇的抗氧化剂所消除。质谱分析表明，甲萘醌与巯基抗氧化剂GSH直接相互作用。美那酮完全抑制Con a诱导的淋巴细胞ERK、JNK和nf - κ B的活化。它还显著降低了同基因CD4+T细胞的稳态驱动增殖。此外，甲萘醌显著延缓了小鼠移植物抗宿主病的发病率和死亡率。甲萘醌抑制植物血凝素诱导的人外周血单核细胞细胞因子的产生。这些结果表明，甲萘醌对细胞氧化还原的干扰是导致淋巴细胞反应显著抑制的原因。
Recent investigations suggest that cellular redox status may play a key role in the regulation of several immune functions. Treatment of lymphocytes with vitamin K3 (menadione) resulted in a significant decrease in cellular GSH/GSSG ratio and concomitant increase in the ROS levels. It also suppressed Concanavalin A (Con A)-induced proliferation and cytokine production in lymphocytes and CD4+T cells in vitro. Immunosuppressive effects of menadione were abrogated only by thiol containing antioxidants. Mass spectrometric analysis showed that menadione directly interacted with thiol antioxidant GSH. Menadione completely suppressed Con A-induced activation of ERK, JNK and NF-kappa B in lymphocytes. It also significantly decreased the homeostasis driven proliferation of syngeneic CD4+T cells. Further, menadione significantly delayed graft-vs-host disease morbidity and mortality in mice. Menadione suppressed phytohemagglutinin-induced cytokine production in human peripheral blood mononuclear cells. These results reveal that cellular redox perturbation by menadione is responsible for significant suppression of lymphocyte responses.