Person: AKKOÇ, TUNÇ
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AKKOÇ
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TUNÇ
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Publication Metadata only Treatment with Mycobacterium vaccae ameliorates airway histopathology in a murine model of asthma(OCEAN SIDE PUBLICATIONS INC, 2008) AKKOÇ, TUNÇ; Yazi, Didem; Akkoc, Tunc; Yesil, Ozlem; Ozdernir, Cevdet; Aydogan, Metin; Koksalan, Kaya; Bahceciler, Nerin N.; Barlan, Isil B.The objective of this study was to evaluate the effect of intratracheal (i.t.) or subcutaneous (s.c.) Mycobacterium vaccae treatment on lung histopathology and cytokine responses in a murine model of asthma. BALB/c mice were divided into four groups. To establish an asthma model, Groups I, II and III received intraperitoneal (i.p.) ovalbumin (OVA) and were challenged with i.t. OVA three times (days 41-47). On the same days, mice in Groups I and II were treated with i.t. and s.c. Mycobacterium vaccae, respectively. Mice in Group IV served as controls. On day 49, lungs were taken out for histopathological evaluation. Cytokine levels were determined in splenocyte culture supernatants by ELISA. The thickness of basement membrane and hyperplasic goblet cells in small airways were found to be significantly more in Group III than Group I. Furthermore, smooth muscle and epithelial thickness in small and large airways and hyperplasic goblet cell numbers in all sized airways of this treatment group were not significantly different from controls. Epithelial thickness in medium and large airways, hyperplasic goblet cells in all sized airways, and basement membrane in small and large airways were not significantly different in Group II when compared to controls. OVA-stimulated IL-5 levels was significantly higher in Group I when compared to Group III. OVA-stimulated IL-5 and spontaneous IL-5 levels were significantly higher in Group 11 than Group III. We demonstrate that subcutaneous and intratracheal Mycobacterium vaccae administered along with allergen has an ameliorating effect in the modulation of airway histopathological changes in OVA sensitized mice.Publication Metadata only Transfer of T cells from intranasal ovalbumin-immunized mice ameliorates allergic response in ova-sensitized recipient mice(OCEAN SIDE PUBLICATIONS INC, 2008) AKKOÇ, TUNÇ; Akkoc, Tunc; Eifan, Aarif O.; Aydogan, Metin; Ozkara, Selvinaz; Bahceciler, Nerin N.; Barlan, Isil B.Mucosal immunotherapy is suggested as a treatment strategy for tolerance induction in allergic diseases. The purpose of this study was to determine the effect of transferred splenic T cells from intranasal ovalbumin (OVA)-immunized mice to naive mice before sensitization on its impact of cytokine production and airway histopathology. BALB/c mice in group I received intranasal immunotherapy (days1-6), carboxylfluorescein succinyl ester (CFSE)-labeled splenocytes or splenic T cells were i.v. transferred to naive recipients (group 11) before OVA sensitization. Acute murine asthma model was established by two i.p. OVA injections (days 21 and 28) and seven OVA nebulizations (days 42-48) in groups 1, 11 and III. Groups If[ and IV served as asthma model and control, respectively. CFSE-labeled cells in splenocytes and lymph node lymphocytes, lung histopathology, IL-4, IL-10, and interferon (IFN) gamma cytokines of recipients were analyzed 24 hours after OVA nebulization challenge. CFSE-labeled T cells from group I were detected in spleen and regional lymph nodes of the OVA-sensitized recipients (group 11). Smooth muscle and thickness of airways were less in intranasal OVA immunotherapy and OVA-sensitized recipients when compared with the asthma model (p < 0.05). Area of inflammation was significantly suppressed in OVA-sensitized recipients compared with the asthma model (p < 0.01). IL-10 and IFN-gamma levels in splenocyte supernatants were significantly increased in intranasal immunotherapy and OVA-sensitized recipients compared with asthma model and controls (P < 0.01). IL-4 levels were significantly less in intranasal immunotherapy group and the OVA-sensitized recipient group when compared with asthma the model group (p < 0.05). This study suggests that intranasal immunotherapy with allergens regulates T-cell responses and ameliorates airway histopathology in sensitized mice, hence, encouraging mucosal tolerance induction as a suitable treatment of allergic diseases.Publication Open Access Mesenchymal stem cells differentiate to retinal ganglion-like cells in rat glaucoma model induced by polystyrene microspheres(2023-10-01) ERASLAN, MUHSİN; ÇERMAN, EREN; BOZKURT, SÜHEYLA; AKKOÇ, TUNÇ; ERASLAN M., ÇERMAN E., BOZKURT S., Genç D., Virlan A. T., Demir C. S., Akkoç T., Karaöz E., AKKOÇ T.Aim: The study aimed to evaluate the differentiation ability of intravitreally injected rat bone marrow-derived mesenchymal stem cells (rBM-MSCs) to retinal ganglion-like cells in a polystyrene microsphere induced rat glaucoma model. Materials and Methods: The glaucoma rat model was generated via intracameral injection of 7 microliter polystyrene microspheres. Green fluorescence protein-labeled (GFP) rBM-MSCs were transplanted intravitreally at or after induction of ocular hypertension (OHT), depending on the groups. By the end of the fourth week, flat-mount retinal dissection was performed, and labeled against Brn3a, CD90, GFAP, CD11b, Vimentin, and localization of GFP positive rBM-MSCs was used for evaluation through immunofluorescence staining and to count differentiated retinal cells by flow cytometry. From 34 male Wistar albino rats, 56 eyes were investigated. Results: Flow cytometry revealed significantly increased CD90 and Brn3a positive cells in glaucoma induced and with rBM-MSC injected groups compared to control(P = 0.006 and P = 0.003 respectively), sham-operated (P = 0.007 and P < 0.001 respectively), and only rBM-MSCs injected groups (P = 0.002 and P = 0.009 respectively). Immunofluorescence microscopy revealed differentiation of GFP labeled stem cells to various retinal cells, including ganglion-like cells. rBM-MSCs were observable in ganglion cells, inner and outer nuclear retinal layers in rBM-MSCs injected eyes. Conclusion: Intravitreally transplanted rBM-MSCs differentiated into retinal cells, including ganglion-like cells, which successfully created a glaucoma model damaged with polystyrene microspheres. Promisingly, MSCs may have a role in neuro-protection and neuro-regeneration treatment of glaucoma in the future.Publication Metadata only IFN-gamma stimulation of dental follicle mesenchymal stem cells modulates immune response of CD4(+) T lymphocytes in Der p1(+) asthmatic patients in vitro(ELSEVIER ESPANA SLU, 2019) AKKOÇ, TUNÇ; Genc, D.; Zibandeh, N.; Nain, E.; Arig, U.; Goker, K.; Aydiner, E. K.; Akkoc, T.Background: House dust mite (Dermataphagoides pteronyssinus) is a widespread risk factor in the development of asthma. CD4(+) T lymphocytes have an important role in the pathogenesis of allergic asthma by polarizing to Th2 cells. Objective: We aimed to evaluate the immunoregulatory effects of dental follicle mesenchymal stem cells with and without IFN-gamma stimulation on peripheral blood mononuclear cells of house dust mite sensitive asthmatic patients, and compared those with Dexamethasone as a systemic steroid. Material and methods: PBMC of asthmatic patients and healthy individuals separately cultured with or without DF-MSCs in the presence and absence of IFN-gamma or Der p1 or Dexamethasone for 72 h. CD4(+) T proliferation, cell viability, CD4(+)CD25(+)FoxP3(+) Treg cell frequency and cytokine profiles of PBMC were evaluated via flow cytometry. Results: DF-MSCs suppressed proliferation of CD4(+) T lymphocytes (p(CDmix) < 0.01, p(Derp1) < 0.01, p(IFN) < 0.005) by increasing the number of FoxP3 expressing CD4(+)CD25(+) T regulatory cells (p(CDmix) < 0.005, p(Derp1) < 0.01, p(IFN) < 0.001) and suppressed lymphocyte apoptosis (p(CDmix) < 0.05, p(Derp1) < 0.05, p(IFN) < 0.05), while Dexamethasone increased the apoptosis and decreased Treg cell frequency in asthmatic patients. IFN-gamma stimulation increased the suppressive effect of DF-MSCs and also enhanced the frequency of FoxP3 expressing CD4(+)CD25(+) T regulatory cells. The cytokine levels were regulated by DF-MSCs by reducing IL-4 cytokine levels (p(CDmix) < 0.01, p(Derp1) < 0.05, p(IFN) < 0.05) and upregulating IFN-gamma levels (p(CDmix) < 0.01, p(Derp1) < 0.05, p(IFN) < 0.005) in asthmatic patients. Conclusion: IFN-gamma stimulated DF-MSCs were found to have a high modulatory effect on CD4(+) T cell responses, while Dexamethasone had an apoptotic effect on CD4(+) T cells in asthmatic patients. DF-MSCs may be a new cell-based therapy option for allergic diseases including asthma. (C) 2019 SEICAP. Published by Elsevier Espana, S.L.U. All rights reserved.Publication Metadata only SARS COV-2 PCR+ hastalarının peptivatör ile etkileşimi sonucu hafıza hücrelerinin incelenmesi(2023-05-25) AKSU, MEHMET BURAK; AKKOÇ, TUNÇ; Yurt C., Durmuş E. R., Sarıgül N., Eşme Y., Kılıç S., Tunca Z., Aksu M. B., Akkoç T.Giriş ve Amaç: SARS COV-2 virüsü, CD4+ ve CD8+ T hücrelerini ve B hücrelerini etkileyerek bağışıklığı aktive etmektedir. CD45RA T hücreleri, antijenleri hatırlamaması ile \"naive\" özelliklere sahipken CD45RO T hücreleri, antijenleri hatırlayıp çoğaldıkları için \"bellek\" T hücreleri olarak kabul edilir. Peptivator SARS-CoV-2 Select, SARS-CoV-2 spesifik CD4+ ve CD8+ T hücrelerini in vitro uyararak efektör sitokinlerin salgılanmasına sebep olup SARS-CoV-2 spesifik T hücrelerinin saptanmasına ve izolasyonuna olanak tanır. Bu çalışmadaki amacımız SARS-COV-2 hastalarının kanından elde edilen lenfositlerin peptivatör ile etkileşimi sonucu hafıza hücrelerinin incelenmesidir. Gereç ve Yöntem: Araştırmamız deneysel tiptedir. Marmara Üniversitesi Pendik Eğitim ve Araştırma Hastanesi Göğüs Hastalıkları polikliniğinde yatan Koronavirüs hastaları, araştırmanın evrenini oluşturmaktadır. T.C. Sağlık Bakanlığı Marmara Üniversitesi Pendik Eğitim ve Araştırma Hastanesi Göğüs Hastalıkları polikliniğinde Koronavirüs hastalığı sebebi ile yatan aşılı ve aşısız, PCR pozitif 18- 50 yaş arası 9 hastadan gönüllü olmaları kaydıyla kan örnekleri toplanmıştır. Hastalardan alınan periferik kanların bir kısmı ile tam kan immünfenotipleme analizi yapılmıştır. Hastalardan alınan periferik kanın bir kısmı ile de mononükleer hücre (PKMH) izolasyonu yapılıp uyarımsız (US), CDmix uyarımlı ve peptivatör ile uyarımı sonrasında akım sitometrisi kullanılarak analizi yapılmıştır. Bulgular: Flow sitometri tam kan immünfenotipleme analizlerinde CD45RO+ oranı aşısız olan grupta 93,6 (±6,76), aşılı grupta 94,2 (±6,07) olarak bulunmuştur. Hastalardan elde edilen PKMH’ler; US, CDmix ve Peptivatör ile kültür edildikten sonra flow sitometri analizlerinde US kültürde CD45RO+FoxP3 oranı aşısız grupta 8,29 (±4,62), aşılı grupta 3,5 (±2,19) olarak bulunmuştur. CDmix kültüründe CD45RO+FoxP3 oranı aşısız grupta 32,6 (±32,4), aşılı grupta 18,8 (±18,6) bulunmuştur. Peptivatör kültüründe CD45RO+Foxp3 oranı aşısız grupta 36,2 (±35,5), aşılı grupta ise 7,24 (±5,94) olarak bulunmuştur. Sonuç: COVID-19’da mRNA teknolojisi ile üretilen BioNTech/Pfizer aşısı enfeksiyon geçiren hastalarda hafıza hücre sayılarını aşısızlara göre arttırmaktadır. Peptivatör etkileşimi ise aşılı PCR+ grupta ve aşısız PCR+ grupta immün sistemi etkilediği ve hafıza hücrelerini arttırdığı gözlenmektedir.Publication Metadata only Association between previous enterobiasis and current wheezing: Evaluation of 1018 children(OCEAN SIDE PUBLICATIONS INC, 2007) AKKOÇ, TUNÇ; Bahceciler, Nerin N.; Ozdemir, Cevdet; Kucukosmanoglu, Ercan; Arikan, Cigdem; Over, Ufuk; Karavelioglu, Salim; Akkoc, Tunc; Yazi, Didem; Yesil, Ozlem; Soysal, Ahmet; Bakir, Mustafa; Barlan, Isil B.The aim of this study was to investigate the association between parasitosis and allergy. We surveyed all children aged 4-12 years living in poor hygienic conditions in a shantytown of Istanbul. After obtaining data from the International Study of Asthma and Allergies in Childhood (ISAAC) and an additional questionnaire, performing a skin-prick test (SPT), and determining total IgE, stool and perianal tape specimens were obtained from 1018 participating children. The prevalence of past episodes of wheezing, current wheezing, asthma, and rhinitis was 31, 14.6, 10.7, and 26.2%, respectively. Parasitosis was present in 49.1%, Enterobius vermicularis (23.3%), being the most common. A history of treatment for enterobiasis was present in 37%. Comparison of children with and without current enterobiasis revealed no significant difference in allergic manifestations and SPT results, except for serum total IgE level (p = 0.018), whereas children with previous enterobiasis were more likely to have current wheezing (p = 0.012). Current wheezers were more likely to have previous enterobiasis (p = 0.01) and a higher maternal employment level (p = 0.036) when compared with those without. According to logistic regression analysis, covariables significantly positively related with current wheezing were previous enterobiasis (p = 0.003) and being : 5 years of age (p = 0.043), whereas being the first child of the family (p = 0.043) was negatively related. A previous infection with E. vermicularis was found to potentiate current wheezing in a population living in a shantytown in Istanbul.Publication Metadata only Effects of different detergent-containing children's toothpastes on the viability, osteogenic and chondrogenic differentiation of human dental periodontal ligament stem cells and gingival stem cells in vitro(CHURCHILL LIVINGSTONE, 2021) AKKOÇ, TUNÇ; Birant, Sinem; Duran, Yazgul; Gokalp, Muazzez; Akkoc, Tunc; Seymen, FigenBackground: Detergents are the most commonly used compounds in toothpastes due to their foaming and cleaning peoperties. This study aimed to investigate the effects of children's toothpastes with different detergent content on the viability, the osteogenic and chondrogenic differentiation potentials of human mesenchymal stem cells. Methods: The necessary tissues for human periodontal ligament mesenchymal stem cells (hPDLMSCs) and human gingival mesenchymal stem cells (hGMSCs) isolation were obtained during extraction of 10 impacted third molar teeth. The viability of the cells stimulated with different concentratiaons of Colgate, Sensodyne, Splat, Nenedent, Perlodent toothpaste solutions and complete Dulbocco's modified eagle medium (control group) were evaluated by using the flow cytometer. In addition, the osteogenic and chondrogenic differentiation potential of human gingival and periodontal ligament mesenchymal stem cells exposed to toothpaste solutions were examined morphologically. Datas were analyzed with IBM SPSS V23. One way ANOVA test was used to determine the differences between the groups for multiple comparisons, while the Tukey post-hoc test was used for pair wise comparisons in determining which groups differed. Results: A higher percentage of cell viability was detected in Control group at 20 %, 50 % and 80 % (p= 0.000) on hGMSCs. After the Control group, the highest cell viability ratios were observed in the detergent-free Splat group (p = 0.000) followed by the Sensodyne experimental group containing CABP (p= 0.000). While the cell viability rates in Nenedent group was found significantly higher than the Perlodent group at other concentrations except for 20 % concentration (p = 0.000). Colgate group had the lowest percentage of cell viability among the experimental groups at all concentrations on hPDMSCs (p = 0.000). The highest live cell ratios was detected in Control group (p = 0.000), followed by Splat and Sensodyne groups (p = 0.000). The cell viability ratios at 50 % concentration were higher in Perlodent group than Nenedent group (p = 0.000). The highest osteogenic and chondrogenic differentiation potential of mesenchymal stem cells stimulated with different toothpaste was determined in Control and Splat group. Conclusions: As a result of the findings, it was observed that toothpaste containing SLS had a more negative effect on the viability of the cells and the differentiation potentials than the other groups.Publication Metadata only Adoptive transfer of splenocytes from immunotherapy, group ameliorating the histopathological changes and increased IL-10 and IFN-g levels in the recipient mice(MOSBY-ELSEVIER, 2007) AKKOÇ, TUNÇ; Akkoc, T.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 Asthma immunotherapy and treatment approaches with mesenchymal stem cells(FUTURE MEDICINE LTD, 2020) AKKOÇ, TUNÇ; Akkoc, Tunc; Genc, DenizAsthma is a chronic inflammatory disease of the airways where exaggerated T helper 2 immune responses and inflammatory mediators play a role. Current asthma treatment options can effectively suppress symptoms and control the inflammatory process; however, cannot modulate the dysregulated immune response. Allergen-specific immunotherapy is one of the effective treatments capable of disease modification. Injecting allergens under the skin in allergen-specific immunotherapy can reduce asthma and improve the sensitivity of the lungs, however, has a risk of severe reactions. Mesenchymal stem cells have immunoregulatory activity with their soluble mediators and contact dependent manner. In this review, we focus on the current treatment strategies with mesenchymal stem cells in asthma as a new therapeutic tool and compare those with immunotherapy.