Notch-1 Signaling Mediated Dendritic Cells - Induced Autologous NK Cell Proliferation and Cytotoxicity Activity to Cancer Cell
Keywords:
Dendritic cells, NK cells, Proliferation, Cytotoxicity, Notch-1Abstract
Natural killer (NK) cells mediated immune responses via cytotoxic activity, or secreting cytokines. The interaction of NK cells with dendritic cells (DCs) contributes to NK cell-mediated anti-tumor or anti-microbial responses. However, the cellular and molecular mechanisms for controlling DC-mediated NK cell cytotoxicity interaction are largely unknown. Here, we showed an involvement of Notch-1 signaling interaction in augmenting NK cell cytotoxicity mediated by DCs. Stimulation of DCs from 6 healthy donors with ipopolysaccharide (LPS) could induce Notch-1 receptor and enhance NK cell proliferation (64.71±1.89%) and their cytotoxicity activity (42.18±1.04%) against K562 cells (human erythroleukemic cell line). DC-mediated NK cell cytotoxicity was suppressed by Notch-1 inhibitor, a γ-secretase inhibitor, (11.91±0.62%), as compared to the LPS treated-DCs (p < 0.05, paired t-test). These results suggested a possible mechanism of DCs mediated NK cell expansion and cytotoxicity regarding to Notch-1 receptor, at least in part. These findings provided an insight that the modulation of Notch-1 signaling could be a strategy to eradicate tumors or to suppress NK cell-mediated diseases.
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