TY - JOUR AU - Márton, Rege Anna AU - Sebők, Csilla AU - Mackei, Máté AU - Tráj, Patrik AU - Vörösházi, Júlia AU - Kemény, Ágnes AU - Neogrády, Zsuzsanna AU - Mátis, Gábor TI - Pap12-6 : A host defense peptide with potent immunomodulatory activity in a chicken hepatic cell culture JF - PLOS ONE J2 - PLOS ONE VL - 19 PY - 2024 IS - 5 PG - 19 SN - 1932-6203 DO - 10.1371/journal.pone.0302913 UR - https://m2.mtmt.hu/api/publication/34865841 ID - 34865841 AB - In the fight against antimicrobial resistance, host defense peptides (HDPs) are increasingly referred to as promising molecules for the design of new antimicrobial agents. In terms of their future clinical use, particularly small, synthetic HDPs offer several advantages, based on which their application as feed additives has aroused great interest in the poultry sector. However, given their complex mechanism of action and the limited data about the cellular effects in production animals, their investigation is of great importance in these species. The present study aimed to examine the immunomodulatory activity of the synthetic HDP Pap12-6 (PAP) solely and in inflammatory environments evoked by lipoteichoic acid (LTA) and polyinosinic-polycytidylic acid (Poly I:C), in a primary chicken hepatocyte-non-parenchymal cell co-culture. Based on the investigation of the extracellular lactate dehydrogenase (LDH) activity, PAP seemed to exert no cytotoxicity on hepatic cells, suggesting its safe application. Moreover, PAP was able to influence the immune response, reflected by the decreased production of interleukin (IL)-6, IL-8, and "regulated on activation, normal T cell expressed and secreted"(RANTES), as well as the reduced IL-6/IL-10 ratio in Poly I:C-induced inflammation. PAP also diminished the levels of extracellular H2O2 and nuclear factor erythroid 2-related factor 2 (Nrf2) when applied together with Poly I:C and in both inflammatory conditions, respectively. Consequently, PAP appeared to display potent immunomodulatory activity, preferring to act towards the cellular anti-inflammatory and antioxidant processes. These findings confirm that PAP might be a promising alternative for designing novel antimicrobial immunomodulatory agents for chickens, thereby contributing to the reduction of the use of conventional antibiotics. LA - English DB - MTMT ER - 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 - CONF AU - Csikós, Eszter AU - Sarah, Shubail AU - Kemény, Ágnes AU - Margita, Szilágyi-Utczás AU - Horváth, Györgyi TI - Effect of wintergreen essential oil and its solution in acute dermatitis in vivo model T2 - 53rd International Symposium on Essential Oils, September 13-16, 2023 - Milazzo, Messina, Italy - Book of Abstracts PY - 2023 SP - 92 UR - https://m2.mtmt.hu/api/publication/34867366 ID - 34867366 LA - English DB - MTMT ER - TY - CONF AU - Shubail, Sarah AU - Csikós, Eszter AU - Kemény, Ágnes AU - Jaber, Areej AU - Szilágyi-Utczás, Margita AU - Horváth, Györgyi ED - Ormai, Edit ED - Balázs, Viktória Lilla ED - Ollmann, Tamás TI - Kontakt dermatisz lehetséges kezelési módja növényi kivonatokkal T2 - Előadás-kivonatok: XXII. Grastyán Konferencia Tanuljunk egymástól! PY - 2023 SP - 11 UR - https://m2.mtmt.hu/api/publication/34867181 ID - 34867181 LA - Hungarian 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 -