Novel synthetic immunostimulators with a thiazolidin-4-one ring promote the cytotoxicity of human NK Cells via ERK1/2 activation in vitro

To investigate how the novel synthetic immunostimulators (CH1a, CH2a, CH1b and CH2b) with a core substructure of thiazolidin-4-one ring influence the function of human natural killer (NK) cells in vitro, first, we obtained highly purified and viable NK cells from peripheral blood mononuclear cells (PBMCs) by a magnetic cell sorter (MACS). Then, the cytotoxicity and proliferative capacity of NK cells were explored after treatment with CH1a, CH2a, CH1b and CH2b. Moreover, the production of IFN-γ and TNF-α was also analyzed. We found that CH1b and CH2b could induce a significant enhancement of cytotoxicity and cytokine production including IFN-γ and TNF-α by NK cells. However, CH1b and CH2b could hardly promote the proliferation of NK cells. In immunoblotting analysis assay, we found that ERK 1/2 could be significantly phosphorylated after treatment with CH1b and CH2b, while the same phenomenon did not emerge after blockade with PD098059, the specific inhibitor of ERK1/2 signaling pathways. Taken together, we can conclude that CH1b and CH2b can elevate the cytotoxicity probably via ERK 1/2 activation.