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Öğe Attenuation of Antibody Response and Elevation of CD4+CD25+Foxp3+ Treg cell Frequency During Chronic Liver Fibrosis(Wiley, 2017) Canpolat, Esra; Karaca, Mete; Kayhan, Basak; Kayhan, Burcak; Bayindir, Yasar; Yilmaz, Sezai[Abstract Not Available]Öğe Chronic liver fibrosis induction in aging causes significant ultra-structural deterioration in liver and alteration on immune response gene expressions in liver-spleen axis(Taylor & Francis Inc, 2024) Karaca, Zeynal Mete; Karaca, Gamze; Kayhan, Basak; Gul, Mehmet; Ersan, Veysel; Bag, Harika Gozukara; Yesilada, ElifThe relationship between damage to the liver and spleen by aging and the immune response status in these two organs, which are anatomically and immunologically interconnected, is unknown. The authors investigated the histopathological, ultrastructural, and immunological effects of aging in young and aged fibrotic mice by using an experimental model. Four groups were planned, with 10 mice in each experimental group. The levels of fibrosis and ultrastructural destruction in the liver were determined by alpha-SMA staining and TEM analysis. Expression levels of immunity genes (Il2, Il4, Il6, Il10, Il12, Il17, Tnf, Ifng, Tgfb1, Gata3, Rorc, Tbx21, Foxp3, Ccl2, Ccr2, Cxcr3, Pf4, Cxcl10) were carried out by qRT-PCR. While structural disorders were detected in the mitochondria of aged healthy group, cellular destruction in the fibrosis-induced elderly group was at a dramatic level. Fibrosis induction in aged mice caused an elevation in the expression of chemokines (CCl2, CXCL10, CCR2) and cytokine (IL-17a) genes that induce autoinflammatory response in the liver. Unlike the cellular pathology and genes activated in fibrosis in youth and the natural occurrence of fibrosis with aging, induction of fibrosis during aging causes deterioration in the liver and expression of genes responsible for autoimmunity in both the liver and spleen.Öğe Dexmedetomidine ameliorates TNBS-induced colitis by inducing immunomodulator effect(Academic Press Inc Elsevier Science, 2013) Kayhan, Gulay Erdogan; Gul, Mehmet; Kayhan, Basak; Gedik, Ender; Ozgul, Ulku; Kurtoglu, Elcin Latife; Durmus, MahmutBackground: Since sedatives are often administered to immune-compromised and critically ill patients, our understanding of immunomodulation by sedation will be critical. Dexmedetomidine, a selective alpha(2)-adrenergic receptor agonist, is often used for sedation and analgesia especially in intensive care units. There are conflicting and little data concerning both the effect and the mechanism of dexmedetomidine on immune response. In our study, we aimed to investigate the effect of dexmedetomidine on immune system at two different doses (5 mu g.kg(-1) and 30 mu g.kg(-1)) during inflammatory bowel disease by using an experimental model, which resembles both systemic and local inflammation. Methods: The effect of dexmedetomidine on the course of inflammatory bowel disease was investigated by measuring macroscopic and microscopic parameters. We investigated pro-inflammatory Th1, Th2, and Th17 cytokine levels in serum samples to analyze systemic immune response. Following this, local immune response was investigated by measuring cytokine levels in the presence of dexmedetomidine in spleen cell culture. Results: Dexmedetomidine administration led to amelioration of all disease associated pathological manifestations. According to our in vitro and in vivo results, dexmedetomidine shows anti-inflammatory effect by increasing IL-4 and IL-10 levels responsible from anti-inflammatory response via Th2 pathway. Moreover, we showed for the first time in the study that dexmedetomidine administration reduces IL-23, which is responsible from initiation of inflammatory response via Th17 pathway. Conclusions: Dexmedetomidine can have beneficial effect on preoperative or postoperative inflammatory bowel disease patients in intensive care units by down-regulating inflammatory immune response not only in systemic circulation but also in tissue-specific manner. (c) 2013 Elsevier Inc. All rights reserved.Öğe The effect of atorvastatin and its role on systemic cytokine network in treatment of acute experimental colitis(Informa Healthcare, 2011) Aktunc, Erol; Kayhan, Basak; Arasli, Mehmet; Gun, Banu Dogan; Barut, FigenInflammatory bowel diseases are characterized by disabilities in gastrointestinal system and defects in mucosal immune system. Statins are 3-hydroxy-3-methyl glutaryl coenzyme A reductase inhibitor and are used to treat hypercholesterolemia in patients with coronary artery and atherosclerotic diseases. Recent studies have demonstrated that statins have immunomodulatory role by effecting different pathways in immune system. In this study, we investigated the effect of atorvastatin and its mechanism on systemic immune response in treatment of trinitrobenzene sulfonic acid (TNBS)-induced colitis mice. We observed that atorvastatin significantly suppressed the severity of TNBS-induced colitis in BALB/c mice. This was manifested in reduced rectal bleeding, decrease in colon length, reduction of histological damage, and improved survival. Concurrently, we investigated the immunomodulatory role of atorvastatin on systemic immune system. We investigated the proinflammatory (IL-1 alpha, IL-6, TNF-alpha), Th1 (IFN-gamma, IL-2), Th2 (IL-4, IL-5, IL-10), and Th17 (IL-17, IL-23) cytokine levels in serum samples of colitis and atorvastatin-administered mice. We discovered that administration of atorvastatin significantly down-regulates systemic TNF-a level and Th17 cytokine levels. Furthermore, atorvastatin treatment switches Th1 type T-cell response toward/to Th2 (IL-4, IL-10) type response.Öğe Effects of interactions between various fats and active/passive phases on postprandial inflammation in rats(Taylor & Francis Ltd, 2016) Otlu, H. Gul; Kayhan, Basak; Guldur, TayfunThe circadian clock controls number of behavioral and physiological processes during daily light/dark cycle including inflammation and vascular injury. However, how reciprocal interaction of dietary fats and light/dark cycle affects postprandial inflammation is currently unknown. To this end, effects of various dietary fats given to rats by gavaging either in light or dark phase on postprandial inflammation were compared. Sunflower oil load activated greater number of inflammatory CD markers in passive phase whereas the butter load in active phase compared to their counter phase. The inflammatory influence of fish oil load appeared to be mostly confined to passive phase. Differences found between the levels of some of the inflammatory markers in active and passive phases of normal fed rats were altered by fat/oil administrations. We conclude that influences of dietary fats/oils on postprandial inflammatory changes might depend not only on their fatty acid compositions but also on their ingestion times.Öğe Effects of Noopept on Oxidative Stress Related Parameters in the Streptozotocin-Induced Diabetes Model(Wiley, 2022) Gurbuz, Perihan; Duzova, Halil; Kayhan, Basak; Cig, Bilal; Naziroglu, Mustafa; Akatli, Ayse Nur[Abstract Not Available]Öğe Effects of reciprocal interactions between various dietary fats and circadian phases on postprandial hyperlipidemia in rats(Taylor & Francis Ltd, 2018) Satilmis, Basri; Kayhan, Basak; Guldur, TayfunExpression levels of various intestinal proteins involved in postprandial lipoprotein assembly as well as plasma triglyceride concentration exhibit daily oscillations indicating circadian control. The length of the carbon chain and degree and position of unsaturation of fatty acids influence triglyceride secretion by the enterocytes. To this end, effects of reciprocal interactions of various single fats/oil (olive oil, fish oil or butter) gavaging either in active or passive phase were investigated in rats. Fat/oil gavaged in the active phase of circadian rhythm resulted in higher postprandial serum triglyceride levels compared to that in the passive phase. Moreover, olive oil led to higher MTP activity and apo B-48 gene expression, while fish oil gavaging caused more prominent apo B-48 and MTP gene expression when they were given in the passive phase. The present results indicate that circadian time at which fat or oil gavaged once might exert influence on postprandial lipoprotein synthesis/assembly.Öğe The expression levels of genes involved in JNK signalingdecrease by aging in the liver(2022) Karaca, Zeynal; Karaca, Gamze; Kayhan, Basak; Kuştepe, Elif KayhanAim: The c-Jun NH2-terminal kinases (JNK) signaling pathway is an important signaling pathway in liver regeneration. it was planned to investigate the expression levels of Mitogen Activated Protein Kinase Kinase (MKK)-4 and -7 (MKK7), which are mediator molecules involved in the JNK signaling pathway and Activating Transcription Factor (ATF) 2 transcription factor genes, which are in the last stage of the signaling pathway, in liver tissues in young and old mice. In addition, it was aimed to examine the ultrastructural changes caused by aging in hepatocytes. Material and Methods: We examined MKK4, MKK7 and ATF2 expression levels by using Real Time Polymerase Chain Reaction (RT-qPCR) method. Transmission electron microscopy (TEM) was used to observe the ultrastructural changes of hepatocytes. Results: While MKK4 and ATF2 gene expressions reduced in the liver of aged mice, MKK7 gene expression did not change. In TEM examinations, granular endoplasmic reticulum loss and mitochondrial damage were observed in elderly individuals. Conclusion: According to these results, spontaneous liver damage that can be seen in aged subjects may be caused by disruption in cellular signaling pathways and organelle damage in hepatocytes.Öğe False negative results in luminex panel reactive antibody identification assay: Should we be alert on them?(2021) Karaca, Mete; Ersan, Veysel; Kayhan, Basak; Yilmaz, SezaiAim: Panel Reactive Antibodies (PRA) analysis is important not only in virtual cross-match of donors and recipients but also in follow-up of recipients immune response after transplantation. Although bead based tests give faster and more reliable, it may have false positive and negative results. We investigated HLA groups of patients with false negative results and the frequencies of anti-HLA antibodies in all three false negative situations.Materials and Methods: PRA results of all patients were divided into 3 groups according to negative controls and samples results. First one is negative controls were false negative and samples were false negative (1st Situation); second one is negative controls were false negative but samples were true negative (2nd Situation); third one is negative controls were true negative but samples were false negative (3rd Situation). All serum samples were tested by bead based Luminex assay.Results: While anti-HLA-A68, A24, A32 were the most frequent antibodies for the first situation, anti-HLA-A03,24,32 were the most frequent three antibodies for the second situation. In case of anti-HLA-B antibodies; anti-HLA-B38, B44, B48 were detected for the first situation, and anti-HLA-B44, B58, B49 were detected for the second situation. In case of class II antibodies; we detected anti-HLA-DRB110, DRB115 and DRB151 antibodies as the most frequent three antibodies at 1st situation. Frequencies of anti-HLA antibodies of 120 patients with false negative results were determined in serum samples. In case of 3rd situation, while anti-A23, A68, A24; anti-B06, B04, B39 and anti-Cw07 were the most frequent anti-HLA Class I antibodies, anti-HLA DQ07, DQ05, DQ04 and anti-HLA-DRB152, DRB113, DRB153 were the most frequent HLA-Class II antibodies detected in serum samples.Conclusion: Samples with false negative PRA results should be repeated and these samples should be recorded in the laboratory for internal control system.Öğe False negative results in luminex panel reactive antibodyidentification assay: Should we be alert on them?(2021) Karaca, Zeynal Mete; Ersan, Veysel; Kayhan, Basak; Yilmaz, SezaiAim: Panel Reactive Antibodies (PRA) analysis is important not only in virtual cross-match of donors and recipients but also in follow-up of recipients immune response after transplantation. Although bead based tests give faster and more reliable, it may have false positive and negative results. We investigated HLA groups of patients with false negative results and the frequencies of antiHLA antibodies in all three false negative situations.Materials and Methods: PRA results of all patients were divided into 3 groups according to negative controls and samples results. First one is negative controls were false negative and samples were false negative (1st Situation); second one is negative controls were false negative but samples were true negative (2nd Situation); third one is negative controls were true negative but samples were false negative (3rd Situation). All serum samples were tested by bead based Luminex assay.Results: While anti-HLA-A68, A24, A32 were the most frequent antibodies for the first situation, anti-HLA-A03,24,32 were the most frequent three antibodies for the second situation. In case of anti-HLA-B antibodies; anti-HLA-B38, B44, B48 were detected for the first situation, and anti-HLA-B44, B58, B49 were detected for the second situation. In case of class II antibodies; we detected anti-HLA-DRB110, DRB115 and DRB151 antibodies as the most frequent three antibodies at 1st situation. Frequencies of anti-HLA antibodies of 120 patients with false negative results were determined in serum samples. In case of 3rd situation, while anti-A23, A68, A24; anti-B06, B04, B39 and anti-Cw07 were the most frequent anti-HLA Class I antibodies, anti-HLA DQ07, DQ05, DQ04 and anti-HLA-DRB152, DRB113, DRB153 were the most frequent HLA-Class II antibodies detected in serum samples.Conclusion: Samples with false negative PRA results should be repeated and these samples should be recorded in the laboratory for internal control system.Öğe Histological and Biochemical Effects of Dexmedetomidine on Liver during an Inflammatory Bowel Disease(Informa Healthcare, 2015) Gul, Mehmet; Kayhan, Basak; Elbe, Hulya; Dogan, Zumrut; Otlu, AliInflammation in the liver is an extraintestinal manifestation that is frequently seen during inflammatory bowel diseases (IBD). The authors investigated histopathologycal, ultrastructural and antioxidant effects of dexmedetomidine (Dex) on liver during trinitrobenzene sulfonic acid (TNBS)-induced inflammatory bowel disease. Thirty-two BALB/c mice were divided (n = 8) as follows: control; Dex (dexmedetomidine) (30 mu g/kg) for 6 days; TNBS 150 mu L, TNBS_ethanol (50% w/v) intrarectally; TNBS_Dex. The histopathological and ultrastructural changes were evaluated. The levels of malondialdehyde (MDA), activity of antioxidant enzymes (GPx and SOD) were measured in liver tissue. Induction of colitis induced histopathological and ultrastructural changes of damage in liver. Those changes were markedly reduced in the TNBS_Dex group and that reduction was even significant in comparison to the TNBS group. MDA levels were significantly higher in the TNBS group and dexmedetomidine significantly elevated SOD levels in the TNBS_Dex group. These results suggest that the administration of dexmedetomidine reduces the histopathological and ultrastructural damage and increases the defense capacity against oxidative damage on liver in this IBD mice model.Öğe Immune Response in the Liver under Conditions of Infection, Malignancy, and Transplantation(Hindawi Ltd, 2014) Kayhan, Basak; Ozdamar, Sukru Oguz; Padberg, Winfried; Kayabas, Uner; Aharoni, Rina; Mirshahidi, Saied[Abstract Not Available]Öğe Influence of Lipoxin-A4 Treatment on Cytokine, Chemokine Genes Expression, and Phenotypic Distribution of Lymphocyte Subsets During Experimental Liver Fibrosis(Aves, 2022) Karaca, Zeynal Mete; Kurtoglu, Elcin Latife; Gul, Mehmet; Kayhan, BasakObjective: Lipoxins are anti-inflammatory, pro-resolving molecules that are secreted by immune cells such as neutrophils and macrophages. Lipoxins are a metabolite of the arachidonic acid pathway that resolve inflammation in fibrotic liver by producing several anti-inflammatory molecules. In this study, phenotypic distribution activation markers of lymphocytes in the spleen and expression levels of chemokines (chemokine (C-X-C motif) receptor 3, chemokine (C-X-C motif) ligand 10) cytokines (interferon gamma, tumor necrosis factor alpha, interleukin-6, interleukin-10) in the liver of lipoxin A4-treated fibrotic mice were investigated. Materials and methods: Liver fibrosis was induced in BALB/c mice by thioacetamide administration. Lipoxin A4 was administered during last 2 weeks of induction. Fibrosis level was determined by using Knodell scoring. Lymphocytes were identified by flow-cytometry. Expression levels of genes were measured by quantitative real time polymerase chain reaction in liver homogenates. Results: Lipoxin A4 treatment caused an elevation of T-lymphocyte percentage in the spleen. Interestingly, administration of lipoxin A4 significantly reduced B-lymphocyte population in spleen of fibrotic group. CD8(+) cytotoxic T cell frequency significantly reduced in thioacetamide-induced mice; however, lipoxin A4 administration increased that percentage significantly. Lipoxin A4 treatment significantly reduced frequency of activated (CD8(+)CD69(+)) cytotoxic T cells. Expression levels of chemokines significantly reduced in the liver after lipoxin A4 treatment. While expression levels of interferon gamma, tumor necrosis factor alpha. and interleukin-6 significantly reduced in the liver after lipoxin A4 treatment, an anti-inflammatory cytokine interleukin-10 expression was almost at similar levels in all experimental groups. Conclusion: Lipoxin A4 performs its anti-inflammatory effect by reducing the frequency of activated T cells and expression levels of chemokines cytokines responsible from inflammatory immune response in the liver.Öğe Is hepatitis-B immunization effective during chronic liver fibrosis? Investigation of secretory and cellular immune responses on an experimental model(Taylor & Francis Ltd, 2023) Kayhan, Basak; Karaca, Zeynal Mete; Canpolat, Esra; Ersan, Veysel; Gul, Mehmet; Yologlu, Saim; Yilmaz, SezaiObjective Adults with end-stage of chronic liver diseases have lower antibody titers after hepatitis-B vaccination. We have less amount of knowledge about the effect of non-viral cause chronic liver fibrosis on vaccination. In this study, we investigated the effect of non-viral chronic liver fibrosis on hepatitis B vaccine and the effect of tetanous toxoid co-administration at the level of humoral and cellular immune responses in an experimental model. Methods Hepatitis B vaccine was administered either alone or in combination with tetanus toxoid in thioacetamide-induced fibrotic BALB/c mice. Fibrosis level was determined by Knodell scoring. Anti-HBsAg, biochemical parameters, inflammatory (IL-1 beta, TNF-alpha), and anti-inflammatory (IL-10) cytokine levels were investigated in serum samples by automated systems and ELISA; respectively. Frequencies of activated lymphocytes were determined in flow cytometer. Results Antibody titers significantly decreased after immunization of fibrotic mice. However, co-administration of toxoid significantly elevated antibody titer. The percentage of CD19(+)CD69(+) B lymphocytes was found to be lower in vaccinated fibrotic group compared to vaccinated naive group. Simultaneous administration of toxoid significantly increased the frequencies of CD4(+) and CD8(+) T cells expressing CD69 and CD127. Interestingly, CD19(+)CD5(+)CD1(high) Breg cells were significantly reduced in the group vaccinated with hepatitis B vaccine and toxoid, simultaneously. The reduction in Breg percentage did not expose a significant decrease in the level of IL-10. Conclusion Non-viral chronic liver fibrosis causes a reduction on specific antibody level after vaccination. Reduction on Breg cell frequency may have an effect on elevation of antibody level after co-administration of tetanus toxoid.Öğe Lipoxin A4 Improves Ultrastructural View of Liver and Reduces Expression Levels of MKK4 and TGF-? During Thioacetamide (TAA) Induced Fibrosis(Wiley, 2017) Kurtoglu, Elcin; Kayhan, Basak; Gul, Mehmet; Kayhan, Burcak; Akdogan, Meral; Yilmaz, Sezai[Abstract Not Available]Öğe Mystery of Immune Response in Relapsed Brucellosis: Immunophenotyping and Multiple Cytokine Analysis(Galenos Yayincilik, 2016) Kayhan, Basak; Kayabas, Uner; Kolgelier, Servet; Otlu, Baris; Gul, Mehmet; Kurtoglu, Elcin Latife; Bayindir, YasarIntroduction: Brucella spp. are intracellular bacteria that may cause acute, subacute and chronic infections. Despite optimum antibiotic treatment, relapse of brucellosis occurs in some patients. There is less amount of knowledge about immune response in relapse of brucellosis. Materials and Methods: Twenty patients with acute brucellosis, 16 patients with relapsed brucellosis and as a control group 20 healthy volunteers were enrolled in this study to explore the immune response variation during relapse of brucellosis. The distribution of peripheral blood mononuclear cells was investigated by flow cytometry and level of various cytokines involved in inflammatory and anti-inflammatory response were measured by enzyme-linked immunosorbent assay in serum samples. Results: The most prominent data in phenotyping examination was the significant reduction (1.45 times) in the percentage of activated T cell (CD3(+) human leukocyte antigen-DR+) population in the relapse group in comparison to the acute brucellosis group. However, percentage of activated T cell population in the relapse group was 2.59 times higher than in healthy controls (p< 0.01). We observed a significant reduction in inflammatory cytokines interleukin (IL)-6, IL-18, interferon-gamma and IL-17 in relapsed patients in comparison to patients with acute brucellosis. While there was no significant difference in IL-15 and tumor necrosis factor-alpha levels between relapse and acute brucellosis groups, the levels of these two cytokines were significantly higher in the relapse group than in healthy subjects. In case of anti-inflammatory cytokines, while IL-4 levels increased significantly only in relapse group, IL-10 levels increased both in acute and relapse brucellosis group in comparison to healthy controls. Interestingly, we observed 2.87 times elevation in IL-4 levels in the relapse group in comparison to acute brucellosis (p< 0.01). Similarly; IL-10 levels increased 2.09 times in patients with relapsed brucellosis patients in comparison to acute brucellosis (p< 0.01). Conclusion: Elevation of regulatory cytokines in systemic immune system and reduction of activated T cell frequency occur during the relapse of brucellosis. These results may contribute to understanding the immunopathology in the systemic circulation during relapse of brucellosis.Öğe The relationship between caspase-1 related inflammasome expression and serum inflammatory cytokine levels during acute brucellosis(Kare Publ, 2019) Karaca, Gamze; Karaca, Zeynal Mete; Kayhan, Basak; Bayindir, Yasar; Kayabas, Uner; Toplu, Sibel; Elmasdag, SirvanOBJECTIVE: Brucellosis is a zoonotic disease caused by Brucella in domestic and wild animals. It also causes systemic diseases with the involvement of different parts of the human body. An efficient innate immune response is crucial to cure brucellosis with optimum antibiotic treatment. The inflammasomes are innate immune system receptors and sensors that regulate the activation of cysteine-dependent aspartate specific protease-1 (caspase-1) and caspase-1-induced cell death process known as pyroptosis. The aim of the present study was to investigate the expression levels of CASPASE-1 and associated inflammasomes AIM2, NLRP3, and NLRC4 to analyze their relationship with the inflammatory cytokine interleukin (IL)-1 beta, IL-18, and interferon-gamma (IFN-gamma) in peripheral blood samples of patients with acute brucellosis with healthy controls. METHODS: Peripheral blood samples were obtained from 20 healthy volunteers and 20 patients with acute brucellosis. RNA and serum samples were isolated to examine the expression levels of AIM2, NLRP3, NLRC4, and CASPASE-1 by real-time polymerase chain reaction, and IL-1 beta, IL-18, and IFN-gamma were measured by enzyme-linked immunosorbent assay. RESULTS: In the acute brucellosis group, AIM2 and NLRC4 expressions were significantly higher than in healthy volunteers. A significant increase on caspase-1 expression in patients with acute brucellosis was not observed. Serum IL-18 and IFN-gamma levels were significantly higher in patients with acute brucellosis than in healthy controls. CONCLUSION: Caspase-1-related inflammasomes are sufficiently activated to induce the secretion of cytokines, such as IFN-gamma and IL-18, to induce cellular immune response. Caspase-1 activation level should be investigated at different periods of disease in a group with high number of patients to understand the role of pyroptosis and caspase-1 in brucellosis.
