In-vitro evaluation of effects of mesenchymal stem cells on tlr3, tlr7/8 and tlr9-activated natural killer cells
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Date
2021
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Abstract
Objectives: In this study, it was aimed to investigate the immunomodulatory effects of Mesenchymal stem cells (MSCs) on Natural Killer (NK) cells activated by Toll-like receptor (TLR) agonists. Methods: MDA-MB-231, MCF-7 and NK-92 cells were induced with TLR3, TLR7/8 and TLR9 agonists and co-cultured with MSCs. Alterations in IFN-γ, TNF-α, Granzyme-b and Perforin expressions were determined by qPCR method, CD69 and CD107a expressions were determined by flow cytometry, and cytotoxicity was determined by MTT-assay. Results: All TLR agonists significantly increased the expressions of the IFN-γ, TNF-α, Granzyme-b, Perforin, CD69 and CD107a in-vitro. We determined that the cytokine, cytotoxic molecules, and activation markers of NK-92 cells interact-ing with breast tumor cells significantly increased by TLR3 and TLR9 agonists. However, suppression rather than activation occurred on the NK-92 cells due to the simultaneous induction of the immunosuppressive effects of MSCs by these agonists. On the other hand, the TLR7/8 agonists provided a low NK-92 induction, however, the inhibitory effects of MSCs were not triggered. Therefore, it provided a more significant activation than TLR3 and TLR9 agonists. Conclusion: Our findings suggested that TLR7/8 agonists may be a better choice to induce antitumor effects of NK cells in a tumor tissue rich in MSCs. © 2021 by Eurasian Journal of Medicine and Oncology.
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CD69 antigen , gamma interferon , granzyme B , lysosome associated membrane protein 1 , perforin , toll like receptor 3 , toll like receptor 7 , toll like receptor 8 , toll like receptor 9 , tumor necrosis factor , Article , cell activation , cell function , cell interaction , coculture , controlled study , human , human cell , human tissue , immunomodulation , immunosuppressive treatment , in vitro study , MCF-7 cell line , MDA-MB-231 cell line , mesenchymal stem cell , natural killer cell , NK-92 cell line , protein expression , real time polymerase chain reaction , tumor immunity