Vitamin K3 suppressed inflammatory and immune responses in a redox-dependent manner

被引:33
作者
Checker, Rahul [1 ]
Sharma, Deepak [1 ]
Sandur, Santosh K. [1 ]
Khan, Nazir M. [1 ]
Patwardhan, Raghavendra S. [1 ]
Kohli, Vineet [2 ]
Sainis, Krishna B. [1 ]
机构
[1] Bhabha Atom Res Ctr, Biomed Grp, Modular Labs, Radiat Biol & Hlth Sci Div, Bombay 400085, Maharashtra, India
[2] Bhabha Atom Res Ctr, Biomed Grp, Modular Labs, Div Med, Bombay 400085, Maharashtra, India
关键词
NF-kappa B; cytokines; lymphocytes; GVHD; GSH; NF-KAPPA-B; HOMEOSTASIS DRIVEN PROLIFERATION; SIGNALING PATHWAYS; OXIDATIVE STRESS; ALPHA KINASE; T-CELLS; ACTIVATION; PLUMBAGIN; GLUTATHIONYLATION; PHOSPHORYLATION;
D O I
10.3109/10715762.2011.585647
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:975 / 985
页数:11
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