Natural killer cell-mediated cytotoxicity is increased by a type II arabinogalactan from Anoectochilus formosanus.

This study investigated the effects of a type II arabinogalactan from Anoectochilus formosanus (AGAF) on natural killer (NK) cell-mediated cytotoxicity and the possible underlying mechanisms. This study reported that sustained exposure to AGAF increased NK-92MI cell-mediated cytotoxicity in a time- and concentration-dependent manner, as characterized according to the cellular lactic dehydrogenase leakage from K562 leukemia cells. Additionally, antibody neutralization studies have reported that interferon (IFN)-γ, but not perforin or tumor necrosis factor-α, released by NK-92MI NK cells is crucial in enhancing cytotoxicity through an autocrine loop. In this study, AGAF was further demonstrated to induce IFN-γ expression, increasing the susceptibility to NK-92MI cell-mediated cytotoxicity through the toll-like receptor (TLR)-2, TLR4, extracellular signal-regulated kinase, p38 mitogen-activated protein kinase, and nuclear factor-κB pathways. A pharmacological study revealed that Janus kinase 2/signal transducers and activators of the signal transducers and of transcription 3 signaling are involved in IFN-γ-induced NK cell-mediated cytotoxicity.