Title

Activation of NK cell cytotoxicity by the natural compound 2,3-butanediol

ORCiD

David M. Ojcius: 0000-0003-1461-4495

Document Type

Article

Publication Title

Journal of Leukocyte Biology

ISSN

0741-5400

Volume

92

Issue

4

DOI

10.1189/jlb.0112024

First Page

807

Last Page

814

Publication Date

10-1-2012

Abstract

The natural compound 2,3-BTD has diverse physiological effects in a range of organisms, including acting as a detoxifying product of liver alcohol metabolism in humans and ameliorating endotoxin-induced acute lung injury in rats. In this study, we reveal that 2,3-BTD enhances NK cell cytotoxic activity in human pNK cells and NK92 cells. Treatment of NK cells with 2,3-BTD increased perforin expression in a dose-dependent manner. This was accompanied by elevated JNK and ERK1/2 MAPK activities and enhanced expression of NKG2D/NCRs, upstream signaling molecules of the MAPK pathways. The 2,3-BTD effect was inhibited by pretreatment with inhibitors of JNK (SP) or ERK1/2 (PD) or by depleting NKG2D/NCRs or JNK1 or ERK2 with siRNA. These results indicate that 2,3-BTD activates NK cell cytotoxicity by NKG2D/NCR pathways and represent the first report of the 2,3-BTD effect on activation of innate immunity cells.