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 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 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.Publication Metadata only Predictors for the severity of bronchial hyperreactivity in childhood asthma(AMER THORACIC SOC, 2001) AKKOÇ, TUNÇ; Bahceciler, NN; Arikan, C; Akkoc, T; Barlan, IBBronchial hyperreactivity (BHR) is a common characteristic of asthma and is shown to be a risk factor in the development and outcome of asthma. In this study, we aimed to assess the risk factors at referral for the severity of BHR, which was determined at the end of a mean of 3 yr of follow-up in 98 children with asthma (mean (+/- SD) age, 11.0 (+/- 3.4) yr, male/female = 50/48]. We also evaluated the cross-sectional risk factors for the severity of BHR in the observed children. Information on risk factors at referral was collected from the computer records of the patients followed by an end-of-study visit. Lung function, skin-prick, and bronchial provocation tests were done and total serum IgE level was measured on this visit. The relationship between BHR and risk factors was investigated by multiple linear regression analysis. A lower level of FEV1% at referral was found to be an important predictor of more severe BHR at the end of the follow-up. None of the other risk factors evaluated predicted the severity of current BHR. We concluded that decreased lung function at referral is associated with a more severe BHR determined at the end of a 3-yr follow-up in children with asthma.Publication Open Access Clinical efficacy and immunological mechanisms of sublingual and subcutaneous immunotherapy in asthmatic/rhinitis children sensitized to house dust mite: an open randomized controlled trial(WILEY, 2010-05-06) AKKOÇ, TUNÇ; Eifan, A. O.; Akkoc, T.; Yildiz, A.; Keles, S.; Ozdemir, C.; Bahceciler, N. N.; Barlan, I. B.Background In children, the clinical efficacy and immunological mechanisms of sublingual immunotherapy (SLIT) compared with subcutaneous immunotherapy (SCIT) is still to be elucidated. Objectives To compare SLIT, SCIT and pharmacotherapy in relation to clinical efficacy and immunological mechanisms that govern its effect in asthmatic/rhinitis children who were sensitized to house dust mite (HDM). Methods In this single centre, prospective, randomized, controlled, open labelled, three parallel group trial, 48 patients mono-sensitized to HDM were randomized to receive either SLIT (n = 16), SCIT (n = 16) or pharmacotherapy alone (n = 16). Symptom, medication and visual analogue score (VAS) were collected and bronchial-nasal hyper-reactivity, skin prick tests, total-specific IgE were performed at baseline and 12 months after treatment. In addition, peripheral blood mononuclear cells were cultured with recombinant Der p 1 and Bet v 1 extracts and allergen-specific IL-4, IL-5, IL-13, IFN-gamma, IL-10, and TGF-beta secretions were measured. Results SLIT and SCIT demonstrated a significant reduction of total rhinitis and asthma symptom score, total medication score, VAS and skin reactivity to HDM (P<0.05) when compared with pharmacotherapy. A significant reduction of serum-specific HDM-IgE in SCIT and SLIT were observed. Moreover, titrated nasal provocative dose significantly increased in both immunotherapy groups when compared with the pharmacotherapy group. No adverse effects were reported in SLIT, while two patients demonstrated serious adverse events in SCIT. After 1 year of treatment, Der p 1-driven IL-10 significantly increased in SLIT compared with pharmacotherapy, whereas Bet v 1-driven TGF-beta (negative control) increased significantly in SLIT only. No changes were observed for Th1-Th2 cytokines. Conclusion Both SLIT and SCIT demonstrated clinical improvement compared with pharmacotherapy in asthma/rhinitis children sensitized to HDM.Publication Metadata only Impact of Mycobacterium vaccae immunization on lung histopathology in a murine model of chronic asthma(WILEY, 2003) AKKOÇ, TUNÇ; Ozdemir, C; Akkoc, T; Bahceciler, NN; Kucukercan, D; Barlan, IB; Basaran, MMBackground Therapeutic modalities of asthma have not been proved to be successful in reversing the already established chronic changes of airways. Objective We aimed to determine the impact of heat-killed Mycobacterium vaccae immunization, a potent Th1 stimulant, on chronic changes of asthma. Methods Newborn BALB/c mice were divided into three groups; mice in M. vaccae group received 10(7) colony-forming units (CFU)/50 muL of heat-killed M. vaccae subcutaneously on days 3, 14 and 42 before the development of chronic asthma model, whereas mice in control and chronic asthma groups received saline. Subsequently, mice in M. vaccae and chronic asthma groups were administered 10 mug/100 muL of ovalbumin (OVA) on days 43, 45, 47, 49, 51, 53 and 55 intraperitoneally, and 20 mug/10 muL of OVA on days 83, 86 and 89 intratracheally. Mice in control group received saline on the same days. Results Comparison of M. vaccae and chronic asthma groups showed statistically significant differences in goblet cell numbers, thickness of basement membrane and subepithelial smooth muscle of small, medium and large airways and epithelial thickness of medium airways. There was no significant difference between the control and M. vaccae groups except for goblet cell numbers of medium and large airways, and epithelial thickness of medium airways. Conclusion Results of our study suggested that immunization by M. vaccae of newborn mice would prevent some of the chronic changes of airways due to asthma.Publication Metadata only No association between tuberculin skin test and atopy in a bacillus Calmette-Guerin vaccinated birth cohort(WILEY, 2009) AKKOÇ, TUNÇ; Eifan, Aarif O.; Akkoc, Tunc; Ozdemir, Cevdet; Bahceciler, Nerin N.; Barlan, Isil B.Previously, an inverse association was suggested between mycobacterial infection and atopy. We aimed to determine the association between tuberculin skin test (TST) and allergic manifestations in a birth cohort where all infants were vaccinated with bacillus Calmette-Guerin (BCG) at birth. Newborns were enrolled randomly and prospectively followed up for a period of 5 yr. Information on family history and environmental factors was obtained at birth, International Study of Asthma and Allergies in Childhood asthma questionnaire, physical examination, skin prick test to common inhalant and food allergens and TST were performed at 2 and 5 yr of age. Positive TST reactivity was defined as an induration of >= 10 mm. A total of 399 newborns were enrolled, 293 and 125 were available for a followup visit at 2 and 5 yr of age respectively. The prevalence of ever asthma, rhinitis and allergen sensitization tended to increase while eczema decreased with time. No significant association was found between TST reactivity and ever and current wheeze, doctor diagnosed asthma or atopic sensitization both at 2 and 5 yr of age. This prospectively designed birth cohort study did not confirm the previously suggested inverse correlation between TST reactivity and atopic sensitization or any allergic manifestations in Turkish children vaccinated with BCG at birth.Publication Metadata only Treatment with chitin microparticles is protective against lung histopathology in a murine asthma model(WILEY, 2006) AKKOÇ, TUNÇ; Ozdemir, C.; Yazi, D.; Aydogan, M.; Akkoc, T.; Bahceciler, N. N.; Strong, P.; Barlan, I. B.Chitin, a natural polysaccharide extracted from shrimp, is a potent T and B cell adjuvant when delivered in the form of chitin microparticles and can shift a polarized T-helper type 2 (Th2) immune response towards a Th1 response. We investigated the beneficial effects of the intranasal application of chitin microparticles in newborn mice before and after the establishment of a model of allergic asthma. Mice were grouped as asthma (A), primary prevention (PP), treatment (T), primary prevention+treatment (PPT) and control (C) groups. All mice except controls were sensitized with ovalbumin intraperitoneally and challenged intratracheally to establish the asthma model. Mice in the PP and PPT groups received chitin microparticles intranasally during the newborn period before sensitization. Mice in the PPT and T groups received intranasal chitin microparticles after challenge. Airway histopathology was evaluated in all groups. All of the airway histopathologic parameters of small and medium-sized airways of the T and PPT groups were significantly ameliorated when compared with the asthma model group. In the large airways, thicknesses of basement membrane, epithelium and subepithelial smooth muscle layers of the PPT group and basement membrane thicknesses of the T group were also significantly lower compared with the asthma model group. Comparison of the PP group with the asthma model group revealed significantly reduced goblet cell numbers and significantly reduced epithelial and basement membrane thicknesses in small and medium airways, in addition to significantly reduced basement membrane thicknesses in the medium-sized airways. Intranasal application of microgram quantities of chitin microparticles had a beneficial effect in preventing and treating histopathologic changes in the airways of asthmatic mice.Publication Open Access Animal models of asthma(2010-01-01) AKKOÇ, TUNÇ; AKKOÇ T.Allergic disease such as asthma, rhinitis, and eczema are increasing prevelance and affect up to 15% of population in Westernized countries. Among them, asthma is a chronic inflammatory disease of airways and the underlying physiological and immunological processes are not fully understood. Mouse models of asthma dupicates many features of human asthma, including airway hyperreactivity, andairway inflammation. Therefore, relevant models for asthma are important to understand the mechanism of disease and therapeutical approach. In this article, basicly various animal models of asthma and some theraputic approaches are disscussed.Publication Metadata only Dental follicle mesenchymal stem cells down-regulate Th2-mediated immune response in asthmatic patients mononuclear cells(WILEY, 2018) ÖZEN, AHMET OĞUZHAN; Genc, D.; Zibandeh, N.; Nain, E.; Gokalp, M.; Ozen, A. O.; Goker, M. K.; Akkoc, T.BackgroundAsthma is a chronic inflammatory disease in which inflammatory responses have the polarisation of CD4(+) T cells to Th2 cells. Dental follicle mesenchymal stem cells (DFSCs) have strong anti-inflammatory properties comparable to other mesenchymal stem cells. ObjectiveWe investigated the immunomodulatory effects of DFSCs on CD4(+) T helper cell responses of asthmatic patients and compared the results with those obtained with asthmatic subjects on immunotherapy and with healthy individuals. MethodPeripheral blood mononuclear cells (PBMC) were isolated from immunotherapy naive asthmatics, asthmatics on subcutaneous Der p1 immunotherapy and from healthy individuals. PBMC were pre-conditioned with anti-CD3/anti-CD28 mAbs, Der p1 or IFN- in the presence and absence of DFSCs and analysed for T cell viability and proliferation, CD4(+)CD25(+)FOXP3(+) regulatory T cell frequencies, cytokine expression, and GATA3, T bet and FoxP3 expressions. Neutralisation of TGF- and blockade of IDO and PGE2 pathways were performed to determine suppressive signalling pathways of DFSCs. ResultsDental follicle mesenchymal stem cells suppressed proliferative responses of CD4(+) T lymphocytes and increased the frequency of Treg cells. DFSCs decreased effector and effector memory CD4(+) T cell phenotypes in favour of naive T cell markers. DFSCs decreased IL-4 and GATA3 expression and increased IFN-, T-bet and IL-10 expression in asthmatics. Costimulatory molecules were suppressed in monocytes with DFSCs in the cocultures. DFSCs down-regulated inflammatory responses via IDO and TGF- pathways in asthmatic patients. ConclusionDental follicle mesenchymal stem cells suppressed allergen-induced Th2-cell polarisation in favour of Th1 responses and attenuated antigen-presenting cell co-stimulatory activities. These studies suggest that DFSC-based cell therapy may provide pro-tolerogenic immunomodulation relevant to allergic diseases such as asthma.