Activation of NK cell cytotoxicity by the natural compound 2,3-butanediol.
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.
Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Taiwan, Republic of China.
Hsin-Chih
HC
Lai
Chih-Jung
CJ
Chang
Chun-Hung
CH
Yang
Ya-Jing
YJ
Hsu
Chang-Chieh
CC
Chen
Chuan-Sheng
CS
Lin
Yu-Huan
YH
Tsai
Tsung-Teng
TT
Huang
David M
DM
Ojcius
Ying-Huang
YH
Tsai
Chia-Chen
CC
Lu
D002072:Butylene Glycols / Q000494:pharmacology*; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000502:physiology; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000502:physiology; D007694:Killer Cells, Natural / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects*; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000502:physiology; D054353:Perforin / Q000235:genetics
D002072:Butylene Glycols; C527085:KLRK1 protein, human; D055655:NK Cell Lectin-Like Receptor Subfamily K; D054353:Perforin; C026978:2,3-butylene glycol; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases