title: Vitamin K3 suppressed inflammatory and immune responses in a redox-dependent manner.
abstract: 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-κB 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.
authors.affiliation: Radiation Biology & Health Sciences Division, Bhabha Atomic Research Centre,Modular Laboratories, Trombay, Mumbai 400 085, India.
authors.forename: Rahul
authors.initials: R
authors.lastname: Checker
authors.forename: Deepak
authors.initials: D
authors.lastname: Sharma
authors.forename: Santosh K
authors.initials: SK
authors.lastname: Sandur
authors.forename: Nazir M
authors.initials: NM
authors.lastname: Khan
authors.forename: Raghavendra S
authors.initials: RS
authors.lastname: Patwardhan
authors.forename: Vineet
authors.initials: V
authors.lastname: Kohli
authors.forename: Krishna B
authors.initials: KB
authors.lastname: Sainis
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000276:immunology*; D008214:Lymphocytes / Q000187:drug effects* / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010084:Oxidation-Reduction / Q000187:drug effects; D013329:Structure-Activity Relationship; D024483:Vitamin K 3 / Q000494:pharmacology*
chemical_list: D024483:Vitamin K 3