Notch-1 Signaling Mediated Dendritic Cells - Induced Autologous NK Cell Proliferation and Cytotoxicity Activity to Cancer Cell

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Supaporn Suparak
Kanokwan Ngueanchanthong
Busarawan Sriwanthana
Somchai Sangkitporn

Abstract

          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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