@article{MTMT:35083838, title = {Mild Hyperthermia-Induced Thermogenesis in the Endoplasmic Reticulum Defines Stress Response Mechanisms}, url = {https://m2.mtmt.hu/api/publication/35083838}, author = {Dukic, Barbara and Ruppert, Zsófia and Tóth, Erzsébet Melinda and Hunya, Ákos and Czibula, Ágnes and Bíró, Péter and Tiszlavicz, Ádám and Péter, Mária and Balogh, Gábor and Erdélyi, Miklós and Timinszky, Gyula and Vigh, László and Gombos, Imre and Török, Zsolt}, doi = {10.3390/cells13131141}, journal-iso = {CELLS-BASEL}, journal = {CELLS}, volume = {13}, unique-id = {35083838}, abstract = {Previous studies reported that a mild, non-protein-denaturing, fever-like temperature increase induced the unfolded protein response (UPR) in mammalian cells. Our dSTORM super-resolution microscopy experiments revealed that the master regulator of the UPR, the IRE1 (inositol-requiring enzyme 1) protein, is clustered as a result of UPR activation in a human osteosarcoma cell line (U2OS) upon mild heat stress. Using ER thermo yellow, a temperature-sensitive fluorescent probe targeted to the endoplasmic reticulum (ER), we detected significant intracellular thermogenesis in mouse embryonic fibroblast (MEF) cells. Temperatures reached at least 8 °C higher than the external environment (40 °C), resulting in exceptionally high ER temperatures similar to those previously described for mitochondria. Mild heat-induced thermogenesis in the ER of MEF cells was likely due to the uncoupling of the Ca2+/ATPase (SERCA) pump. The high ER temperatures initiated a pronounced cytosolic heat-shock response in MEF cells, which was significantly lower in U2OS cells in which both the ER thermogenesis and SERCA pump uncoupling were absent. Our results suggest that depending on intrinsic cellular properties, mild hyperthermia-induced intracellular thermogenesis defines the cellular response mechanism and determines the outcome of hyperthermic stress.}, year = {2024}, eissn = {2073-4409}, orcid-numbers = {Hunya, Ákos/0000-0002-4547-9284; Czibula, Ágnes/0000-0003-4461-2773; Bíró, Péter/0000-0001-8103-6248; Tiszlavicz, Ádám/0009-0008-4830-0594; Erdélyi, Miklós/0000-0002-9501-5752} } @article{MTMT:32733913, title = {α/β-Peptides as Nanomolar Triggers of Lipid Raft-Mediated Endocytosis through GM1 Ganglioside Recognition}, url = {https://m2.mtmt.hu/api/publication/32733913}, author = {Hetényi, Anasztázia and Szabó, Enikő and Imre, Norbert and Nath Bhaumik, Kaushik and Tököli, Attila and Füzesi, Tamás and Hollandi, Réka and Horváth, Péter and Czibula, Ágnes and Monostori, Éva and Deli, Mária Anna and Martinek, Tamás}, doi = {10.3390/pharmaceutics14030580}, journal-iso = {PHARMACEUTICS}, journal = {PHARMACEUTICS}, volume = {14}, unique-id = {32733913}, abstract = {Cell delivery of therapeutic macromolecules and nanoparticles is a critical drug development challenge. Translocation through lipid raft-mediated endocytic mechanisms is being sought, as it can avoid rapid lysosomal degradation. Here, we present a set of short alpha/beta-peptide tags with high affinity to the lipid raft-associated ganglioside GM1. These sequences induce effective internalization of the attached immunoglobulin cargo. The structural requirements of the GM1-peptide interaction are presented, and the importance of the membrane components are shown. The results contribute to the development of a receptor-based cell delivery platform.}, year = {2022}, eissn = {1999-4923}, orcid-numbers = {Hetényi, Anasztázia/0000-0001-8080-6992; Tököli, Attila/0000-0001-8413-3182; Czibula, Ágnes/0000-0003-4461-2773; Monostori, Éva/0000-0002-7442-3562; Deli, Mária Anna/0000-0001-6084-6524; Martinek, Tamás/0000-0003-3168-8066} } @article{MTMT:32570862, title = {Fehérje méretű molekulák humán sejtekbe juttatása lipid-raft mediált endocitózissal}, url = {https://m2.mtmt.hu/api/publication/32570862}, author = {Hetényi, Anasztázia and Imre, Norbert and Szabó, Enikő and Bodnár, Brigitta and Szkalisity, Ábel and Gróf, Ilona and Bocsik, Alexandra and Deli, Mária Anna and Horváth, Péter and Czibula, Ágnes and Monostori, Éva and Martinek, Tamás}, journal-iso = {BIOKÉMIA}, journal = {BIOKÉMIA: A MAGYAR BIOKÉMIAI EGYESÜLET FOLYÓIRATA}, volume = {45}, unique-id = {32570862}, issn = {0133-8455}, year = {2021}, eissn = {2060-8152}, pages = {67-83}, orcid-numbers = {Hetényi, Anasztázia/0000-0001-8080-6992; Deli, Mária Anna/0000-0001-6084-6524; Czibula, Ágnes/0000-0003-4461-2773; Monostori, Éva/0000-0002-7442-3562; Martinek, Tamás/0000-0003-3168-8066} } @article{MTMT:31126947, title = {Routing Nanomolar Protein Cargoes to Lipid Raft‐Mediated/Caveolar Endocytosis through a Ganglioside GM1‐Specific Recognition Tag}, url = {https://m2.mtmt.hu/api/publication/31126947}, author = {Imre, Norbert and Hetényi, Anasztázia and Szabó, Enikő and Bodnár, Brigitta and Szkalisity, Ábel and Gróf, Ilona and Bocsik, Alexandra and Deli, Mária Anna and Horváth, Péter and Czibula, Ágnes and Monostori, Éva and Martinek, Tamás}, doi = {10.1002/advs.201902621}, journal-iso = {ADV SCI}, journal = {ADVANCED SCIENCE}, volume = {7}, unique-id = {31126947}, abstract = {There is a pressing need to develop ways to deliver therapeutic macromolecules to their intracellular targets. Certain viral and bacterial proteins are readily internalized in functional form through lipid raft‐mediated/caveolar endocytosis, but mimicking this process with protein cargoes at therapeutically relevant concentrations is a great challenge. Targeting ganglioside GM1 in the caveolar pits triggers endocytosis. A pentapeptide sequence WYKYW is presented, which specifically captures the glycan moiety of GM1 (KD = 24 nm). The WYKYW‐tag facilitates the GM1‐dependent endocytosis of proteins in which the cargo‐loaded caveosomes do not fuse with lysosomes. A structurally intact immunoglobulin G complex (580 kDa) is successfully delivered into live HeLa cells at extracellular concentrations ranging from 20 to 160 nm, and escape of the cargo proteins to the cytosol is observed. The short peptidic WYKYW‐tag is an advantageous endocytosis routing sequence for lipid raft‐mediated/caveolar cell delivery of therapeutic macromolecules, especially for cancer cells that overexpress GM1.}, year = {2020}, eissn = {2198-3844}, orcid-numbers = {Hetényi, Anasztázia/0000-0001-8080-6992; Deli, Mária Anna/0000-0001-6084-6524; Czibula, Ágnes/0000-0003-4461-2773; Monostori, Éva/0000-0002-7442-3562; Martinek, Tamás/0000-0003-3168-8066} } @article{MTMT:31598466, title = {Proteomimetic surface fragments distinguish targets by function}, url = {https://m2.mtmt.hu/api/publication/31598466}, author = {Tököli, Attila and Mag, Beáta Zsófia and Bartus, Éva and Wéber, Edit and Szakonyi, Gerda and Simon, Márton and Czibula, Ágnes and Monostori, Éva and Nyitray, László and Martinek, Tamás}, doi = {10.1039/d0sc03525d}, journal-iso = {CHEM SCI}, journal = {CHEMICAL SCIENCE}, volume = {11}, unique-id = {31598466}, issn = {2041-6520}, year = {2020}, eissn = {2041-6539}, pages = {10390-10398}, orcid-numbers = {Tököli, Attila/0000-0001-8413-3182; Bartus, Éva/0000-0001-9976-6978; Wéber, Edit/0000-0002-5904-0619; Szakonyi, Gerda/0000-0002-4366-4283; Czibula, Ágnes/0000-0003-4461-2773; Monostori, Éva/0000-0002-7442-3562; Nyitray, László/0000-0003-4717-5994; Martinek, Tamás/0000-0003-3168-8066} } @article{MTMT:30750520, title = {TMEM203 is a binding partner and regulator of STING-mediated inflammatory signaling in macrophages}, url = {https://m2.mtmt.hu/api/publication/30750520}, author = {Li, Yang and James, Sharmy J and Wyllie, David H and Wynne, Claire and Czibula, Ágnes and Bukhari, Ahmed and Pye, Katherine and Bte Mustafah, Seri Musfirah and Fajka-Boja, Roberta and Szabó, Enikő and Angyal, Adrienn and Hegedűs, Zoltán and Kovács, László and Hill, Adrian V S and Jefferies, Caroline A and Wilson, Heather L and Yongliang, Zhang and Kiss-Tóth, Endre}, doi = {10.1073/pnas.1901090116}, journal-iso = {P NATL ACAD SCI USA}, journal = {PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA}, volume = {116}, unique-id = {30750520}, issn = {0027-8424}, abstract = {Regulation of IFN signaling is critical in host recognition and response to pathogens while its dysregulation underlies the pathogenesis of several chronic diseases. STimulator of IFN Genes (STING) has been identified as a critical mediator of IFN inducing innate immune pathways, but little is known about direct coregulators of this protein. We report here that TMEM203, a conserved putative transmembrane protein, is an intracellular regulator of STING-mediated signaling. We show that TMEM203 interacts, functionally cooperates, and comigrates with STING following cell stimulation, which in turn leads to the activation of the kinase TBK1, and the IRF3 transcription factor. This induces target genes in macrophages, including IFN-β. Using Tmem203 knockout bone marrow-derived macrophages and transient knockdown of TMEM203 in human monocyte-derived macrophages, we show that TMEM203 protein is required for cGAMP-induced STING activation. Unlike STING, TMEM203 mRNA levels are elevated in T cells from patients with systemic lupus erythematosus, a disease characterized by the overexpression of type I interferons. Moreover, TMEM203 mRNA levels are associated with disease activity, as assessed by serum levels of the complement protein C3. Identification of TMEM203 sheds light into the control of STING-mediated innate immune responses, providing a potential novel mechanism for therapeutic interventions in STING-associated inflammatory diseases.}, keywords = {lupus; STIM1; STING; interferon signaling; TMEM203}, year = {2019}, eissn = {1091-6490}, pages = {16479-16488}, orcid-numbers = {Czibula, Ágnes/0000-0003-4461-2773; Fajka-Boja, Roberta/0000-0001-5331-8280; Kovács, László/0000-0003-4457-1430} } @article{MTMT:30802849, title = {Altered Cell Surface N-Glycosylation of Resting and Activated T Cells in Systemic Lupus Erythematosus}, url = {https://m2.mtmt.hu/api/publication/30802849}, author = {Szabó, Enikő and Hornung, Ákos and Monostori, Éva and Bocskai, Márta and Czibula, Ágnes and Kovács, László}, doi = {10.3390/ijms20184455}, journal-iso = {INT J MOL SCI}, journal = {INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES}, volume = {20}, unique-id = {30802849}, issn = {1661-6596}, abstract = {Altered cell surface glycosylation in congenital and acquired diseases has been shown to affect cell differentiation and cellular responses to external signals. Hence, it may have an important role in immune regulation; however, T cell surface glycosylation has not been studied in systemic lupus erythematosus (SLE), a prototype of autoimmune diseases. Analysis of the glycosylation of T cells from patients suffering from SLE was performed by lectin-binding assay, flow cytometry, and quantitative real-time PCR. The results showed that resting SLE T cells presented an activated-like phenotype in terms of their glycosylation pattern. Additionally, activated SLE T cells bound significantly less galectin-1 (Gal-1), an important immunoregulatory lectin, while other lectins bound similarly to the controls. Differential lectin binding, specifically Gal-1, to SLE T cells was explained by the increased gene expression ratio of sialyltransferases and neuraminidase 1 (NEU1), particularly by elevated ST6 beta-galactosamide alpha-2,6-sialyltranferase 1 (ST6GAL1)/NEU1 and ST3 beta-galactoside alpha-2,3-sialyltransferase 6 (ST3GAL6)/NEU1 ratios. These findings indicated an increased terminal sialylation. Indeed, neuraminidase treatment of cells resulted in the increase of Gal-1 binding. Altered T cell surface glycosylation may predispose the cells to resistance to the immunoregulatory effects of Gal-1, and may thus contribute to the pathomechanism of SLE.}, year = {2019}, eissn = {1422-0067}, orcid-numbers = {Monostori, Éva/0000-0002-7442-3562; Czibula, Ágnes/0000-0003-4461-2773; Kovács, László/0000-0003-4457-1430} } @article{MTMT:3190067, title = {Characterization and therapeutic application of canine adipose mesenchymal stem cells to treat elbow osteoarthritis}, url = {https://m2.mtmt.hu/api/publication/3190067}, author = {Kriston-Pál, Éva and Czibula, Ágnes and Gyuris, Z and Balka, Gyula and Seregi, A and Sükösd, Farkas and Süth, Miklós and Kiss-Tóth, E and Haracska, Lajos and Uher, Ferenc and Monostori, Éva}, journal-iso = {CAN J VET RES}, journal = {CANADIAN JOURNAL OF VETERINARY RESEARCH-REVUE CANADIENNE DE RECHERCHE VETERINAIRE}, volume = {81}, unique-id = {3190067}, issn = {0830-9000}, abstract = {Visceral adipose tissue (AT) obtained from surgical waste during routine ovariectomies was used as a source for isolating canine mesenchymal stem cells (MSCs). As determined by cytofluorimetry, passage 2 cells expressed MSC markers CD44 and CD90 and were negative for lineage-specific markers CD34 and CD45. The cells differentiated toward osteogenic, adipogenic, and chondrogenic directions. With therapeutic aims, 30 dogs (39 joints) suffering from elbow dysplasia (ED) and osteoarthritis (OA) were intra-articularly transplanted with allogeneic MSCs suspended in 0.5% hyaluronic acid (HA). A highly significant improvement was achieved without any medication as demonstrated by the degree of lameness during the follow-up period of 1 y. Control arthroscopy of 1 transplanted dog indicated that the cartilage had regenerated. Histological analysis of the cartilage biopsy confirmed that the regenerated cartilage was of hyaline type. These results demonstrate that transplantation of allogeneic adipose tissue-derived mesenchymal stem cells (AT-MSCs) is a novel, noninvasive, and highly effective therapeutic tool in treating canine elbow dysplasia. © 2017, Canadian Veterinary Medical Association. All rights reserved.}, year = {2017}, eissn = {1928-9022}, pages = {73-78}, orcid-numbers = {Czibula, Ágnes/0000-0003-4461-2773; Uher, Ferenc/0000-0001-7997-6142; Monostori, Éva/0000-0002-7442-3562} } @article{MTMT:3024122, title = {Galectin-1 is a local but not systemic immunomodulatory factor in mesenchymal stromal cells}, url = {https://m2.mtmt.hu/api/publication/3024122}, author = {Fajka-Boja, Roberta and Suhajdáné Urbán, Veronika and Szebeni, Gábor and Czibula, Ágnes and Blaskó, Andrea and Kriston-Pál, Éva and Makra, Ildikó and Hornung, Ákos and Szabó, Enikő and Uher, Ferenc and Than, Nándor Gábor and Monostori, Éva}, doi = {10.1016/j.jcyt.2015.12.004}, journal-iso = {CYTOTHERAPY}, journal = {CYTOTHERAPY}, volume = {18}, unique-id = {3024122}, issn = {1465-3249}, abstract = {BACKGROUND AIMS: Mesenchymal stromal cells (MSCs) have powerful immunosuppressive activity. This function of MSCs is attributed to plethora of the expressed immunosuppressive factors, such as galectin-1 (Gal-1), a pleiotropic lectin with robust anti-inflammatory effect. Nevertheless, whether Gal-1 renders or contributes to the immunosuppressive effect of MSCs has not been clearly established. Therefore, this question was the focus of a complex study. METHODS: MSCs were isolated from bone marrows of wild-type and Gal-1 knockout mice and their in vitro anti-proliferative and apoptosis-inducing effects on activated T cells were examined. The in vivo immunosuppressive activity was tested in murine models of type I diabetes and delayed-type hypersensitivity. RESULTS: Both Gal-1-expressing and -deficient MSCs inhibited T-cell proliferation. Inhibition of T-cell proliferation by MSCs was mediated by nitric oxide but not PD-L1 or Gal-1. In contrast, MSC-derived Gal-1 triggered apoptosis in activated T cells that were directly coupled to MSCs, representing a low proportion of the T-cell population. Furthermore, absence of Gal-1 in MSCs did not affect their in vivo immunosuppressive effect. CONCLUSIONS: These results serve as evidence that Gal-1 does not play a role in the systemic immunosuppressive effect of MSCs. However, a local contribution of Gal-1 to modulation of T-cell response by direct cell-to-cell interaction cannot be excluded. Notably, this study serves a good model to understand how the specificity of a pleiotropic protein depends on the type and localization of the producing effector cell and its target.}, year = {2016}, eissn = {1477-2566}, pages = {360-370}, orcid-numbers = {Fajka-Boja, Roberta/0000-0001-5331-8280; Suhajdáné Urbán, Veronika/0000-0003-0393-5891; Szebeni, Gábor/0000-0002-6998-5632; Czibula, Ágnes/0000-0003-4461-2773; Uher, Ferenc/0000-0001-7997-6142; Monostori, Éva/0000-0002-7442-3562} } @article{MTMT:3115599, title = {Mesenchymal stem cells promote macrophage polarization toward M2b-like cells.}, url = {https://m2.mtmt.hu/api/publication/3115599}, author = {Kudlik, Gyöngyi and Hegyi, B and Czibula, Ágnes and Monostori, Éva and Buday, László and Uher, Ferenc}, doi = {10.1016/j.yexcr.2016.08.022}, journal-iso = {EXP CELL RES}, journal = {EXPERIMENTAL CELL RESEARCH}, volume = {348}, unique-id = {3115599}, issn = {0014-4827}, abstract = {Mesenchymal stem or stromal cells (MSCs) act on different components of the immune response including macrophages (MPhis). Therefore this study has been committed to explore how MSCs may modify the effect of MPhi polarization upon an inductive environment using mouse bone marrow (BM)-derived "naive", unpolarized MPhis. Phagocytosis of various MPhi subtypes was different since M1 and M2b showed poorer, while M2a higher rate of phagocytosis. MSCs significantly promoted yeast ingestion by M1 and M2b and diminished it by M2a cells. Under polarizing conditions, MSCs profoundly affected the TNFalpha production of MPhi subtypes since M1 and M2b MPhis produced less and M2a produced higher amount of TNFalpha while the amount of IL-10 was not affected. The most striking effect of MSCs was registered on M2b cells since the inflammatory TNFalpha dominance remarkably shifted to the immunosuppressive IL-10. Prepolarized M1 cells readily converted to M2a and M2b states when polarizing conditions changed from M1 to M2a or M2b induction, respectively. Repolarizing from M1 to M2a resulted in the decline of IL-10 and TNFalpha and defined elevation of Ym1 similar to levels characteristic to M2a primarily polarized from naive BM-MPhis. Similarly, polarization of M1 to M2b MPhis was successful showing increase in IL-10 and reduction in TNFalpha levels characteristic to M2b cells. However, when co-culturing with MSCs, M1-M2a or M1-M2b transition was not affected. Crosstalk between MPhis and MSCs depended on PGE-2 since COX-2 inhibition reduced the effect of MSCs to establish an IL-10-dominant cytokine production by MPhis.}, year = {2016}, eissn = {1090-2422}, pages = {36-45}, orcid-numbers = {Czibula, Ágnes/0000-0003-4461-2773; Monostori, Éva/0000-0002-7442-3562; Buday, László/0000-0003-3518-5757; Uher, Ferenc/0000-0001-7997-6142} }