title: Novel synthetic immunostimulators with a thiazolidin-4-one ring promote the cytotoxicity of human NK cells via ERK1/2 activation in vitro.
abstract: 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.
authors.affiliation: Department of Immunology, School of Medicine, Hebei University, Baoding 071002, China. mengming@hbu.edu.cn
authors.forename: Ming
authors.initials: M
authors.lastname: Meng
authors.forename: Chunxiao
authors.initials: C
authors.lastname: Li
authors.forename: Dongzhi
authors.initials: D
authors.lastname: Chen
authors.forename: Zerui
authors.initials: Z
authors.lastname: Wang
authors.forename: Yang
authors.initials: Y
authors.lastname: Hong
authors.forename: Hua
authors.initials: H
authors.lastname: Chen
authors.forename: Xiaoliu
authors.initials: X
authors.lastname: Li
authors.forename: Jinchao
authors.initials: J
authors.lastname: Zhang
authors.forename: Fu-Sheng
authors.initials: FS
authors.lastname: Wang
mesh_terms: D000276:Adjuvants, Immunologic / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D018920:Coculture Techniques; D003602:Cytotoxicity, Immunologic; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D015151:Immunoblotting; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000201:enzymology / Q000276:immunology*; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000276:Adjuvants, Immunologic; D013844:Thiazoles