TY - CONF AU - Shubail, Sarah AU - Csikós, Eszter AU - Kemény, Ágnes AU - Jaber, Areej AU - Utczás, Margita AU - Horváth, Györgyi ED - Szabó, Szilvia TI - Növényi kivonatok vizsgálata in vivo kontakt dermatisz modellben T2 - Abstract Book of the 7th International Cholnoky Symposium PY - 2024 SP - 25 EP - 25 PG - 1 UR - https://m2.mtmt.hu/api/publication/34795176 ID - 34795176 LA - Hungarian DB - MTMT ER - TY - JOUR AU - Márton, Rege Anna AU - Sebők, Csilla AU - Mackei, Máté AU - Tráj, Patrik AU - Vörösházi, Júlia AU - Kemény, Ágnes AU - Neogrády, Zsuzsa AU - Mátis, Gábor TI - Cecropin A: investigation of a host defense peptide with multifaceted immunomodulatory activity in a chicken hepatic cell culture JF - FRONTIERS IN VETERINARY SCIENCE J2 - FRONT VET SCI VL - 11 PY - 2024 PG - 10 SN - 2297-1769 DO - 10.3389/fvets.2024.1337677 UR - https://m2.mtmt.hu/api/publication/34718275 ID - 34718275 N1 - project no. RRF-2.3.1-21-2022-00001 has been implemented with the support provided by the Recovery and Resilience Facility (RRF), financed under the National Recovery Fund budget estimate, RRF-2.3.1-21 funding scheme. AB - IntroductionHost defense peptides (HDPs) are increasingly referred to as promising candidates for the reduction of the use of conventional antibiotics, thereby combating antibiotic resistance. As HDPs have been described to exert various immunomodulatory effects, cecropin A (CecA) appears to be a potent agent to influence the host inflammatory response.MethodsIn the present study, a chicken primary hepatocyte–non-parenchymal cell co-culture was used to investigate the putative immunomodulatory effects of CecA alone and in inflammatory conditions evoked by polyinosinic-polycytidylic acid (Poly I:C). To examine the viability of the cells, the extracellular lactate dehydrogenase (LDH) activity was determined by colorimetric assay. Inflammatory markers interleukin (IL)-8 and transforming growth factor-ß1 (TGF-ß1) were investigated using the ELISA method, whereas concentrations of IL-6, IL-10, and interferon-γ (IFN-γ) were assayed by Luminex xMAP technology. Extracellular H2O2 and malondialdehyde levels were measured by fluorometric and colorimetric methods, respectively.ResultsResults of the lower concentrations suggested the safe application of CecA; however, it might contribute to hepatic cell membrane damage at its higher concentrations. We also found that the peptide alleviated the inflammatory response, reflected by the decreased production of the pro-inflammatory IL-6, IL-8, and IFN-γ. In addition, CecA diminished the levels of anti-inflammatory IL-10 and TGF-ß1. The oxidative markers measured remained unchanged in most cases of CecA exposure.DiscussionCecA displayed a multifaceted immunomodulatory but not purely anti-inflammatory activity on the hepatic cells, and might be suggested to maintain the hepatic inflammatory homeostasis in Poly I:C-triggered immune response. To conclude, our study suggests that CecA might be a promising molecule for the development of new immunomodulatory antibiotic-substitutive agents in poultry medicine; however, there is still a lot to clarify regarding its cellular effects. LA - English DB - MTMT ER - TY - GEN AU - Nehr-Majoros, Andrea Kinga AU - Bencze, Noémi AU - Payrits, Maja AU - Kemény, Ágnes AU - György, Sétáló Jr. AU - Helyes, Zsuzsanna AU - Szőke, Éva TI - Analgesic effects of cyclodextrin derivatives via modulation of Transient Receptor Potential Ankyrin 1 ion channel function PY - 2024 UR - https://m2.mtmt.hu/api/publication/34577002 ID - 34577002 LA - English DB - MTMT ER - TY - JOUR AU - Sebők, Csilla AU - Tráj, Patrik AU - Mackei, Máté AU - Márton, Rege Anna AU - Vörösházi, Júlia AU - Kemény, Ágnes AU - Neogrády, Zsuzsa AU - Mátis, Gábor TI - Modulation of the immune response by the host defense peptide IDR-1002 in chicken hepatic cell culture JF - SCIENTIFIC REPORTS J2 - SCI REP VL - 13 PY - 2023 IS - 1 PG - 12 SN - 2045-2322 DO - 10.1038/s41598-023-41707-z UR - https://m2.mtmt.hu/api/publication/34133724 ID - 34133724 AB - IDR-1002, a synthetic host defense peptide (HDP), appears to be a potential candidate for the treatment of bacterial infections and the consequent inflammatory response due to its potent immunomodulatory activity. This is of relevance to the emerging issue of antimicrobial resistance in the farming sector. In this study, the effects of IDR-1002 were investigated on a chicken hepatocyte‒non-parenchymal cell co-culture, and the results revealed that IDR-1002 had complex effects on the regulation of the hepatic innate immunity. IDR-1002 increased the levels of both RANTES (Regulated on Activation, Normal T cell Expressed and Secreted) and Macrophage colony stimulating factor (M-CSF), suggesting the peptide plays a role in the modulation of macrophage differentiation, also reflected by the reduced concentrations of interleukin (IL)-6 and IL-10. The pro-inflammatory cytokine release triggered by the bacterial cell wall component lipoteichoic acid (LTA) was ameliorated by the concomitantly applied IDR-1002 based on the levels of IL-6, chicken chemotactic and angiogenic factor (CXCLi2) and interferon (IFN)-γ. Moreover, the production of nuclear factor erythroid 2-related factor 2 (Nrf2), an essential transcription factor in the antioxidant defense pathway, was increased after IDR-1002 exposure, while protein carbonyl (PC) levels were also elevated. These findings suggest that IDR-1002 affects the interplay of the cellular immune response and redox homeostasis, thus the peptide represents a promising tool in the treatment of bacterially induced inflammation in chickens. LA - English DB - MTMT ER - TY - JOUR AU - Tráj, Patrik AU - Sebők, Csilla AU - Mackei, Máté AU - Kemény, Ágnes AU - Farkas, Orsolya AU - Kákonyi, Ákos AU - Kovács, László AU - Neogrády, Zsuzsa AU - Jerzsele, Ákos AU - Mátis, Gábor TI - Luteolin: A Phytochemical to Mitigate S. Typhimurium Flagellin-Induced Inflammation in a Chicken In Vitro Hepatic Model JF - ANIMALS J2 - ANIMALS-BASEL VL - 13 PY - 2023 IS - 8 PG - 15 SN - 2076-2615 DO - 10.3390/ani13081410 UR - https://m2.mtmt.hu/api/publication/33788876 ID - 33788876 AB - The use of natural feed supplements is an alternative tool to diminish the damage caused by certain bacteria, improving animal health and productivity. The present research aimed to investigate the proinflammatory effect of flagellin released from the bacterial flagellum of Salmonella enterica serovar Typhimurium and to attenuate the induced inflammation with luteolin as a plant-derived flavonoid on a chicken primary hepatocyte–non-parenchymal cell co-culture. Cells were cultured in a medium supplemented with 250 ng/mL flagellin and 4 or 16 µg/mL luteolin for 24 h. Cellular metabolic activity, lactate dehydrogenase (LDH) activity, interleukin-6, 8, 10 (IL-6, IL-8, IL-10), interferon-α, γ (IFN-α, IFN-γ), hydrogen peroxide (H2O2) and malondialdehyde (MDA) concentrations were determined. Flagellin significantly increased the concentration of the proinflammatory cytokine IL-8 and the ratio of IFN-γ/IL-10, while it decreased the level of IL-10, indicating that the model served adequate to study inflammation in vitro. Luteolin treatment at 4 µg/mL did not prove to be cytotoxic, as reflected by metabolic activity and extracellular LDH activity, and significantly reduced the flagellin-triggered IL-8 release of the cultured cells. Further, it had a diminishing effect on the concentration of IFN-α, H2O2 and MDA and restored the level of IL-10 and the ratio of IFN-γ/IL-10 when applied in combination with flagellin. These results suggest that luteolin at lower concentrations may protect hepatic cells from an excessive inflammatory response and act as an antioxidant to attenuate oxidative damage. LA - English DB - MTMT ER - TY - CONF AU - Sebők, Csilla AU - Walmsely, Stephanie AU - Tráj, Patrik AU - Mackei, Máté AU - Vörösházi, Júlia AU - Kemény, Ágnes AU - Neogrády, Zsuzsa AU - Mátis, Gábor TI - Immunomodulatory Effects of Chicken Cathelicidin-2 on a Primary Hepatic Cell Co-Culture Model T2 - Proceedings of the 15th International Scientific Conference on Prebiotics, Probiotics, Gut Microbiota and Health, IPC 2022 SN - 9788090836419 PY - 2022 SP - 112 PG - 1 UR - https://m2.mtmt.hu/api/publication/33656412 ID - 33656412 LA - English DB - MTMT ER - TY - JOUR AU - Sebők, Csilla AU - Walmsley, Stephanie AU - Tráj, Patrik AU - Mackei, Máté AU - Vörösházi, Júlia AU - Kulcsárné Petrilla, Janka AU - Kovács, László AU - Kemény, Ágnes AU - Neogrády, Zsuzsa AU - Mátis, Gábor TI - Immunomodulatory effects of chicken cathelicidin-2 on a primary hepatic cell co-culture model. JF - PLOS ONE J2 - PLOS ONE VL - 17 PY - 2022 IS - 10 PG - 18 SN - 1932-6203 DO - 10.1371/journal.pone.0275847 UR - https://m2.mtmt.hu/api/publication/33146759 ID - 33146759 AB - Cathelicidin-2 is an antimicrobial peptide (AMP) produced as part of the innate immune system of chickens and might be a new candidate to combat infection and inflammation within the gut-liver axis. Studying the hepatic immune response is of high importance as the liver is primarily exposed to gut-derived pathogen-associated molecular patterns. The aim of the present study was to assess the effects of chicken cathelicidin-2 alone or combined with lipoteichoic acid (LTA) or phorbol myristate acetate (PMA) on cell viability, immune response and redox homeostasis in a primary hepatocyte-non-parenchymal cell co-culture of chicken origin. Both concentrations of cathelicidin-2 decreased the cellular metabolic activity and increased the extracellular lactate dehydrogenase (LDH) activity reflecting reduced membrane integrity. Neither LTA nor PMA affected these parameters, and when combined with LTA, cathelicidin-2 could not influence the LDH activity. Cathelicidin-2 had an increasing effect on the concentration of the proinflammatory CXCLi2 and interferon- (IFN-)γ, and on that of the anti-inflammatory IL-10. Meanwhile, macrophage colony stimulating factor (M-CSF), playing a complex role in inflammation, was diminished by the AMP. LTA elevated IFN-γ and decreased M-CSF levels, while PMA only increased the concentration of M-CSF. Both concentrations of cathelicidin-2 increased the H2O2 release of the cells, but the concentration of malondialdehyde as a lipid peroxidation marker was not affected. Our findings give evidence that cathelicidin-2 can also possess anti-inflammatory effects, reflected by the alleviation of the LTA-triggered IFN-γ elevation, and by reducing the M-CSF production induced by PMA. Based on the present results, cathelicidin-2 plays a substantial role in modulating the hepatic immune response with a multifaceted mode of action. It was found to have dose-dependent effects on metabolic activity, membrane integrity, and reactive oxygen species production, indicating that using it in excessively high concentrations can contribute to cell damage. In conclusion, cathelicidin-2 seems to be a promising candidate for future immunomodulating drug development with an attempt to reduce the application of antibiotics. LA - English DB - MTMT ER - TY - JOUR AU - Vörös, Imre AU - Onódi, Zsófia AU - Tóth, Viktória AU - Gergely, Tamás G AU - Sághy, Éva AU - Görbe, Anikó AU - Kemény, Ágnes AU - Leszek, Przemyslaw AU - Helyes, Zsuzsanna AU - Ferdinandy, Péter AU - Varga, Zoltán TI - Saxagliptin Cardiotoxicity in Chronic Heart Failure: The Role of DPP4 in the Regulation of Neuropeptide Tone JF - BIOMEDICINES J2 - BIOMEDICINES VL - 10 PY - 2022 IS - 7 PG - 17 SN - 2227-9059 DO - 10.3390/biomedicines10071573 UR - https://m2.mtmt.hu/api/publication/32916736 ID - 32916736 N1 - Cited By :4 Export Date: 31 December 2023 AB - Dipeptidyl-peptidase-4 (DPP4) inhibitors are novel medicines for diabetes. The SAVOR-TIMI-53 clinical trial revealed increased heart-failure-associated hospitalization in saxagliptin-treated patients. Although this side effect could limit therapeutic use, the mechanism of this potential cardiotoxicity is unclear. We aimed to establish a cellular platform to investigate DPP4 inhibition and the role of its neuropeptide substrates substance P (SP) and neuropeptide Y (NPY), and to determine the expression of DDP4 and its neuropeptide substrates in the human heart. Western blot, radio-, enzyme-linked immuno-, and RNA scope assays were performed to investigate the expression of DPP4 and its substrates in human hearts. Calcein-based viability measurements and scratch assays were used to test the potential toxicity of DPP4 inhibitors. Cardiac expression of DPP4 and NPY decreased in heart failure patients. In human hearts, DPP4 mRNA is detectable mainly in cardiomyocytes and endothelium. Treatment with DPP4 inhibitors alone/in combination with neuropeptides did not affect viability but in scratch assays neuropeptides decreased, while saxagliptin co-administration increased fibroblast migration in isolated neonatal rat cardiomyocyte-fibroblast co-culture. Decreased DPP4 activity takes part in the pathophysiology of end-stage heart failure. DPP4 compensates against the elevated sympathetic activity and altered neuropeptide tone. Its inhibition decreases this adaptive mechanism, thereby exacerbating myocardial damage. LA - English DB - MTMT ER - TY - JOUR AU - Csikós, Eszter AU - Csekő, Kata AU - Kemény, Ágnes AU - Draskóczi, Lilla AU - Kereskai, László AU - Kocsis, Béla AU - Böszörményi, Andrea AU - Helyes, Zsuzsanna AU - Horváth, Györgyi TI - Pinus sylvestris L. and Syzygium aromaticum (L.) Merr. & L. M. Perry Essential Oils Inhibit Endotoxin-Induced Airway Hyperreactivity despite Aggravated Inflammatory Mechanisms in Mice. JF - MOLECULES J2 - MOLECULES VL - 27 PY - 2022 IS - 12 PG - 14 SN - 1420-3049 DO - 10.3390/molecules27123868 UR - https://m2.mtmt.hu/api/publication/32907494 ID - 32907494 N1 - Department of Pharmacognosy, Faculty of Pharmacy, University of Pecs, Pecs, H-7624, Hungary Department of Pharmacology and Pharmacotherapy, Medical School, University of Pecs, Pecs, H-7624, Hungary Szentágothai Research Centre, University of Pecs, Pecs, H-7624, Hungary Department of Medical Biology and Central Electron Microscope Laboratory, Medical School, University of Pecs, Pecs, H-7624, Hungary Department of Pathology, Medical School, University of Pecs, Pecs, H-7624, Hungary Department of Medical Microbiology and Immunology, Medical School, University of Pecs, Pecs, H-7624, Hungary Institute of Pharmacognosy, Faculty of Pharmacy, Semmelweis University, Budapest, H-1085, Hungary PharmInVivo Ltd, Pecs, H-7629, Hungary Cited By :2 Export Date: 4 September 2023 CODEN: MOLEF Correspondence Address: Horváth, G.; Department of Pharmacognosy, Hungary; email: horvath.gyorgyi@gytk.pte.hu AB - Scots pine (SO) and clove (CO) essential oils (EOs) are commonly used by inhalation, and their main components are shown to reduce inflammatory mediator production. The aim of our research was to investigate the chemical composition of commercially available SO and CO by gas chromatography-mass spectrometry and study their effects on airway functions and inflammation in an acute pneumonitis mouse model. Inflammation was evoked by intratracheal endotoxin and EOs were inhaled three times during the 24 h experimental period. Respiratory function was analyzed by unrestrained whole-body plethysmography, lung inflammation by semiquantitative histopathological scoring, myeloperoxidase (MPO) activity and cytokine measurements. α-Pinene (39.4%) was the main component in SO, and eugenol (88.6%) in CO. Both SO and CO significantly reduced airway hyperresponsiveness, and prevented peak expiratory flow, tidal volume increases and perivascular edema formation. Meanwhile, inflammatory cell infiltration was not remarkably affected. In contrast, MPO activity and several inflammatory cytokines (IL-1β, KC, MCP-1, MIP-2, TNF-α) were aggravated by both EOs. This is the first evidence that SO and CO inhalation improve airway function, but enhance certain inflammatory parameters. These results suggest that these EOs should be used with caution in cases of inflammation-associated respiratory diseases. LA - English DB - MTMT ER - TY - JOUR AU - Voros, I AU - Onodi, Z. S. AU - Toth, V. E. AU - Gergely, T. AU - Saghy, E. AU - Görbe, Anikó AU - Kemény, Ágnes AU - Leszek, P. AU - Helyes, Zsuzsanna AU - Ferdinandy, Péter AU - Varga, Zoltán TI - Investigation of cardiotoxicity by dipeptidyl-peptidase-4 inhibitors in a human cardiomyocyte cell line as well as in samples from chronic heart failure patients JF - CARDIOVASCULAR RESEARCH J2 - CARDIOVASC RES VL - 118 PY - 2022 IS - Suppl. 1 SP - i117 EP - i117 PG - 1 SN - 0008-6363 DO - 10.1093/cvr/cvac066.109 UR - https://m2.mtmt.hu/api/publication/32907391 ID - 32907391 LA - English DB - MTMT ER -