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

来源：

FREE RADICAL RESEARCH | 2011年 / 45卷 / 08期

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

页码：975 / 985

页数：11

共 30 条

[1] Vitamin K3 Disrupts the Microtubule Networks by Binding to Tubulin: A Novel Mechanism of Its Antiproliferative Activity [J].