title: Natural killer cell-mediated cytotoxicity is increased by a type II arabinogalactan from Anoectochilus formosanus.
abstract: 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.
authors.affiliation: College of Biopharmaceutical and Food Sciences, Department of Cosmeceutics, China Medical University, Taichung, Taiwan, ROC.
authors.forename: Li-Chan
authors.initials: LC
authors.lastname: Yang
authors.affiliation: School of Medicine, Department of Pharmacology, China Medical University, Taichung, Taiwan, ROC.
authors.forename: Ching-Yi
authors.initials: CY
authors.lastname: Lai
authors.affiliation: School of Pharmacy, China Medical University, No. 91 Hsueh Shih Road, Taichung, Taiwan, ROC. Electronic address: wclin@mail.cmu.edu.tw.
authors.forename: Wen-Chuan
authors.initials: WC
authors.lastname: Lin
mesh_terms: D003602:Cytotoxicity, Immunologic; D005685:Galactans / Q000494:pharmacology*; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology*; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000187:drug effects / Q000276:immunology*; D029595:Orchidaceae / Q000737:chemistry*; D015398:Signal Transduction
chemical_list: D005685:Galactans; D007371:Interferon-gamma; C005653:arabinogalactan
keywords: Anoectochilus formosanus; Arabinogalactan; Cytotoxicity; IFN-gamma; Natural killer cells; Polysaccharides