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

2,3‐BTD activates NK cells cytotoxicity by NKG2D/NCRs pathways. 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.