Browsing by Author "Ozdemir, AT"

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    In-Vitro Evaluation of Immunomodulation Effects of Mesenchymal Stem Cell-Derived Exosomes in Refractory Chronic Spontaneous Urticaria
    Ozdemir, AT; Kirmaz, C; Ozgul Ozdemir, RB; Oztatlici, M; Kilicarslan Sonmez, P; Tuglu, MI
    Objective: Approximately half of chronic spontaneous urticaria (CSU) patients are thought to have an autoimmune pathology, and they are resistant to current treatment approaches. Mesenchymal stem cells (MSCs) are adult cells that have been shown to be useful in many autoimmune pathologies due to their immunomodulation properties. This study aimed to investigate the immunomodulatory effects of MSCs, and exosomes isolated from refractory CSU patients.Materials and Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from 5 refractory CSU patients and 5 healthy volunteers. The effects of MSCs isolated from CSU patients and healthy MSCs were compared. Co-culture experiments were performed to evaluate the efficacy of Mesenchymal Stem Cells and exosomes on PBMCs of CSU patients and healthy volunteers. To compare the resulting effects, changes in IFN-gamma, IL-4, IL-10, IL-17a, and TGF-(3 cytokines were detected by the ELISA method. Cell proliferations were detected with the CCK-8 kit.Results: The effects of autologous and allogeneic MSCs on IFN-gamma expressions were similar, both providing significant suppression at all cell ratios. However, IL-4 and IL-10 expression of PBMCs co-cultured with allogeneic MSCs significantly decreased while IL-17a and TGF-(3 expression increased significantly. In addition, our findings indicated that exosomes were capable of significant suppression at low PBMC ratios, regardless of autologous or allogeneic origin, but MSCs were more effective as the number of PBMCs increased.Conclusion: These preliminary findings from in-vitro experiments suggested that allogeneic MSC, or high-dose exosome administration may be a potential approach for treatment in CSU patients, most of whom are regarded as suffering from an autoimmune disease and resistant to current treatments. However, our findings need to be supported by clinical studies.
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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.
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    Prognostic value of serum pregnancy-associated plasma protein A level at the initial ED presentation in elderly patients with CAP
    Golcuk, Y; Golcuk, B; Bilge, A; Korkmaz, A; Irik, M; Hayran, M; Ozdemir, AT; Kurtulmus, Y
    Objective: This study aims to compare serum pregnancy-associated plasma protein A (PAPP-A) levels in surviving and nonsurviving elderly patients with community-acquired pneumonia (CAP), investigating whether PAPP-A is correlated with CAP prediction scores and whether PAPP-A can successfully predict 28-day mortality rates in elderly patients. Methods: This prospective, observational, single-center, cross-sectional study was conducted at the emergency department (ED) of Celal Bayar University Hospital in Manisa, Turkey, between January and September 2014. All patients underwent follow-up evaluations 28 days after admission. The end point was defined as all-cause mortality. Results: A total of 100 elderly patients (mean age, 77.3 +/- 7.6 years [range, 65-94 years]); 60% men) with CAP were enrolled in this study. All-cause mortality at the 28-day follow-up evaluation was 22%. Admission PAPP-A levels were significantly higher in nonsurvivors compared with 28-day survivors (10.3 +/- 4.5 vs 3.8 +/- 2.6 ng/mL, P < .001). A significant and positive correlation between admission PAPP-A levels and pneumonia severity index; confusion, oxygen saturation, respiratory rate, blood pressure, and age 75 years or older; and confusion, urea, respiratory rate, blood pressure, and age older than 65 years scores was found (r = .440, P < .001; r = .395, P < .001; and r = .359, P < .001, respectively). Moreover, we determined that the optimal PAPP-A cutoff for predicting 28-day mortality at the time of ED admission was 5.1 ng/mL, with 77.3% sensitivity and 77.9% specificity. Conclusions: Serum PAPP-A level is valuable for predicting mortality and the severity of the disease among elderly patients with CAP at ED admission. Thus, PAPP-A might play a further role in the clinical assessment of the severity of CAP. (C) 2015 Elsevier Inc. All rights reserved.
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    Interaction between human dental pulpderived mesenchymal stem cells (hDPMSCs) and CD4+T lymphocyte subsets
    Ozdemir, AT; Özdemir, RBO; Kirmaz, C; Eker, SA; Halbutogullari, ZSU; Ozel, C; Karaoz, E