Person: AKKOÇ, TUNÇ
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AKKOÇ
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TUNÇ
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Publication Metadata only Suppressive effect of compact bone-derived mesenchymal stem cells on chronic airway remodeling in murine model of asthma(ELSEVIER SCIENCE BV, 2014) FİLİNTE, DENİZ; Ogulur, Ismail; Gurhan, Gulben; Aksoy, Ayca; Duruksu, Gokhan; Inci, Cigdem; Filinte, Deniz; Kombak, Faruk Erdem; Karaoz, Erdal; Akkoc, TuncNew therapeutic strategies are needed in the treatment of asthma besides vaccines and pharmacotherapies. For the development of novel therapies, the use of mesenchymal stem cells (MSCs) is a promising approach in regenerative medicine. Delivery of compact bone (CB) derived MSCs to the injured lungs is an alternative treatment strategy for chronic asthma. In this study, we aimed to isolate highly enriched population of MSCs from mouse CB with regenerative capacity, and to investigate the impact of these cells in airway remodeling and inflammation in experimental ovalbumin-induced mouse model of chronic asthma. mCB-MSCs were isolated, characterized, labeled with GFP and then transferred into mice with chronic asthma developed by ovalbumin (OVA) provocation. Histopathological changes including basement membrane, epithelium, subepithelial smooth thickness and goblet cell hyperplasia, and MSCs migration to lung tissues were evaluated. These histopathological alterations were increased in ovalbumin-treated mice compared to PBS group (P < 0.001). Intravenous administration of mCB-MSC significantly reduced these histopathological changes in both distal and proximal airways (P < 0.001). We showed that GFP-labeled MSCs were located in the lungs of OVA group 2 weeks after intravenous induction. mCB-MSCs also significantly promoted Treg response in ovalbumin-treated mice (OVA + MSC group) (P < 0.037). Our studies revealed that mCB-MSCs migrated to lung tissue and suppressed histopathological changes in murine model of asthma. The results reported here provided evidence that mCB-MSCs may be an alternative strategy for the treatment of remodeling and inflammation associated with chronic asthma. (C) 2014 Elsevier B.V. All rights reserved.Publication Metadata only Lymphocyte proliferation in common variable immunodeficiency (CVID) patients by carboxyfluorescein succinimidyl ester (CFSE)(2011-01-01) AKKOÇ, TUNÇ; ÖĞÜLÜR, İSMAİL; AYDINER, ELİF; BARIŞ, SAFA; Izgi A., AKKOÇ T., Ogulur I., Tevetoglu A., AYDINER E., BARIŞ S., Bahceciler N., Barlan I.Objective: Common variable immunodeficiency (CVID) is a heterogeneous disease in the group of predominantly antibody deficiencies, which is defined by hypogammaglobulinemia and normal or low level of B cells, and characterized by increased susceptibility to recurrent bacterial infections, autoimmune disorders, and malignancies. In this study, we aimed to investigate the proliferation of the B and T lymphocytes in patients with CVID.Publication Metadata only Allogeneic pluripotent stem cells suppress airway inflammation in murine model of acute asthma(ELSEVIER, 2014) FİLİNTE, DENİZ; Ogulur, Ismail; Gurhan, Gulben; Kombak, Faruk Erdem; Filinte, Deniz; Barlan, Isil; Akkoc, TuncNew strategies are needed to suppress airway inflammation and prevent or reverse airway remodeling in asthma. Reprogramming induced pluripotent stem cells (iPSCs) have the potential of embryonic stem cells (ESCs) and provide a resource for stem cell-based utility. The aim of this study was to evaluate the histopathological and immunomodulatory effects of ESCs and iPSCs for potential allogenic application in a murine model of acute asthma. BALB/c mice were sensitized with alum-absorbed ovalbumin (OVA) and then challenged with 1% aerosolized OVA. 5 x 10(5) ESCs and iPSCs were administrated intranasally on the last day of nebulization. Mice were sacrificed after 24 h, and serum allergen specific antibody level, airway remodeling, cytokine levels in lung supernatants, and eosinophilic infiltration in BAL fluid were examined. As a result, more ESCs and iPSCs integrated into the lungs of mice in OVA groups than those of the controls. Epithelial, smooth muscle and basal membrane thicknesses as well as goblet cell hyperplasia occurring in airway remodeling were significantly suppressed by pluripotent stem cells in both distal and proximal airways. Percentage of eosinophils decreased significantly in BAL fluid as well as serum allergen-specific IgE and IL-4 levels in lung supernatants. On the contrary, regulatory cytokine - IL-10 level - was enhanced. Application of especially ESCs significantly increased the percentage of Treg subsets. Our comparative results showed that i.n. delivery of miRNA-based reprogrammed iPSCs is beneficial in attenuating airway inflammation in a murine model of acute asthma, and that cells also have similar immunomodulatory effects in mice. (C) 2014 Elsevier B.V. All rights reserved.Publication Open Access Investigation of Th17 cell differentiation in immunodeficiencies associated with high IgE levels and/or autoimmunity(2011-01-01) AKKOÇ, TUNÇ; ÖĞÜLÜR, İSMAİL; AYDINER, ELİF; BARIŞ, SAFA; AKKOÇ T., Tevetoglu A., Ogulur I., Izgi A., AYDINER E., BARIŞ S., Bahceciler N., Barlan I.Objective: Hyper IgE Syndrome (HIES) and Common Variably Immunodeficiency (CVID) are immuno-deficiency diseases. HIES is characterized by recurrent skin abscesses, pneumonia, mucocutaneous fungal infections, eczama, eosinophilia and high serum IgE levels. CVID is characterized by recurrent bacterial infections in airways and gastrointestinal tract. In this study, differentiation of Th17 cells were aimed to be investigated in CVID and HIES patients.Publication Metadata only Mouse Bone Marrow Derived Mesenchymal Stem Cells Supress Airway Inflammation In Both Chronic and Acute Murine Asthma Model(MOSBY-ELSEVIER, 2014) FİLİNTE, DENİZ; Akkoc, Tunc; Ogulur, Ismail; Gurhan, Gulben; Aksoy, Ayca; Duruksu, Gokhan; Filinte, Deniz; Kombak, Erdem; Barlan, Isil B.; Karaoz, ErdalPublication Metadata only Investigation of the impact of intravenous injection of mesenchymal stem cells from mouse bone marrow on muscle weakness and immunological parameters in experimental autoimmune myasthenia gravis model(ELSEVIER SCIENCE BV, 2014) ÖĞÜLÜR, İSMAİL; Ulusoy, Canan Aysel; Kucukerden, Melike; Turan, Selin; Gurkan, Gulben; Ogulur, Ismail; Akkoc, Tunc; Tuzun, ErdemPublication Open Access Th17 differentiation in hyper-IgE syndrome; IL-17 secretion and ROR gamma t expression(2013-01-01) AKKOÇ, TUNÇ; ÖĞÜLÜR, İSMAİL; AKKOÇ T., Ogulur I., Tevetoglu A., Izgi A., Hatirnaz-Ng O., Yin-Ng Y., Safa B., Aydiner-Karakoc E.Objective: Hyper-IgE syndrome (HIES) is characterized by susceptibility to infection and low number of Th17 cells. Th17 is believed to be critical in the clearance of fungal and extracellular bacterial infections. Present study investigates the differentiation of Th17 cells by evaluation of interleukin 17 (IL-17) secretion and RAR-related orphan receptor gamma t (ROR gamma t) expression in HIES compared with healthy subjects. Objective: Hyper-IgE syndrome (HIES) is characterized by susceptibility to infection and low number of Th17 cells. Th17 is believed to be critical in the clearance of fungal and extracellular bacterial infections. Present study investigates the differentiation of Th17 cells by evaluation of interleukin 17 (IL-17) secretion and RAR-related orphan receptor gamma t (RORγt) expression in HIES compared with healthy subjects. Method: Three children diagnosed with HIES and 4 healthy subjects were enrolled in the study. HIES scores were evaluated and clinical data of patients were collected from their hospital records. At Th17 polarizing conditions, Th17 differentiation was assessed by the secretion of IL-17 with ELISA and the expression of ROR-γt with real time PCR. Results: HIES (n=3) patients showed significantly lower levels of IL-17 secretion compared to the healthy subjects (n=4) regarding the peripheral blood mononuclear cells (PBMCs) and CD45+RA naive T cells cultured in Th17 differentiating conditions. In addition, phorbol 12-myristate 13-acetate (PMA) and ionomycin stimulated IL-17 levels of healthy group were significantly higher than unstimulated conditions. Moreover, PMA and ionomycin stimulated IL-17 levels of PBMC cultures were significantly higher when compared to unstimulated conditions for both HIES patients and healthy subjects. ROR-γt expression level of stimulated PBMCs for HIES patient was detected nearly half of that of the healthy subject. Conclusion: Evaluation of IL-17 secretion and ROR-γt expression should be performed to determine the patients who are candidates for mutation analyses. Performing these steps and selection of HIES patients without known mutations in our country would provide an opportunity to discover new genetic defects and so new therapeutic approaches in HIES