Browsing by Author "Ozdemir, RBO"

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    In-vitro Evaluation of Effects of Mesenchymal Stem Cells on TLR3, TLR7/8 and TLR9-activated Natural Killer Cells
    Ozdemir, AT; Kirmaz, C; Ozdemir, RBO; Degirmenci, P; Oztatlici, M; Degirmenci, M
    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-gamma, TNF-alpha, 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-gamma, TNF-alpha, Granzyme-b, Perforin, CD69 and CD107a in-vitro. We determined that the cytokine, cytotoxic molecules, and activation markers of NK-92 cells interacting 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.
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    Immunomodulatory Effects of MDA-MB-231-derived Exosome Mimetic Nanovesicles on CD4+ T Cell Line
    Oztatlici, M; Ozdemir, AT; Oztatlici, H; Kucukhuyuk, S; Ozdemir, RBO; Orhan, H; Ozbilgin, K
    Objectives: The aim of this study is to investigate the immunomodulatory effects of MDA-MB-231 cells or MDA-MB231-derived exosome-mimetic nanovesicles (NVs) on CD4+ Jurkat cells. Methods: NVs were produced by the breakdown of MDA-MB-231 cells and the characterization of generated NVs were performed by using direct-ELISA and Flow cytometry methods. We co -cultured CD4+ Jurkat cells with MDA-MB-231 cells or MDA-MB-231-derived NVs for 48 h. Subsequently, expressions of pro -inflammatory and anti-inflammatory cytokines, and related transcription factors of CD4+ Jurkat cells were evaluated by qPCR method. Results: Clustering, which is the indicator of activation, was not seen in the CD4+ Jurkat cells co -cultured with MDAMB-231 cells. However, CD4+ Jurkat cell clusters were observed in the co -culture experiments with all NV concentrations. In addition, it was determined that the expressions of pro -inflammatory cytokines significantly increased while the expressions of anti-inflammatory cytokines was dramatically decreased in the NV -treated groups. On the contrary, opposite results were obtained in CD4+ Jurkat cells co -cultured with MDA-MB-231 cells. Moreover, TNF-alpha and Gata3 expressions were decreased in all groups. Conclusion: These preliminary findings from in -vitro experiments suggested that NVs could be a potential tool in cancer immunotherapy, but our data need to be supported by more comprehensive studies.