Janko Kos

University of Ljubljana

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Vito Türk

Jožef Stefan Institute

I. Harapin

University of Zagreb

Anja Pišlar

University of Ljubljana

Stanislav Gobec

University of Ljubljana

Jerica Sabotič

Jožef Stefan Institute

Nataša Obermajer

University of Pittsburgh

Ana Mitrović

University of Ljubljana

Tamara T. Lah

National Institute of Biology

Milica Perišić Nanut

Jožef Stefan International Postgraduate School

Zala Jevnikar

AstraZeneca (Sweden)

Cooperative Institutions

University of Ljubljana

242

Institut za filozofiju

123

Jožef Stefan Institute

120

Schneeberger (Switzerland)

106

University of Zagreb

Jožef Stefan International Postgraduate School

Ljubljana University Medical Centre

National Institute of Biology

Centre National de la Recherche Scientifique

University of California, Los Angeles

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The role of cathepsin X in cell signaling

Cell Adhesion & Migration (2009)

Janko Kos Zala Jevnikar Nataša Obermajer

Cathepsin X is a lysosomal cysteine protease, found predominantly in cells of monocyte/macrophage lineage. It acts as a monocarboxypepidase and has a strict positional and narrower substrate specificity relative to the other human cathepsins. In our recent studies we identified  β2 subunit of integrin receptors and α and γ enolase as possible substrates for cathepsin X carboxypeptidase activity. In both cases cathepsin X is capable to cleave regulatory motifs at C-terminus affecting the function of targeted molecules. We demonstrated that via activation of β2 integrin receptor Mac-1 (CD11b/CD18) active cathepsin X enhances adhesion of monocytes/macrophages to fibrinogen and regulates the phagocytosis. By activation of Mac-1 receptor cathepsin X may regulate also the maturation of dendritic cells, a process, which is crucial in the initiation of adaptive immunity. Cathepsin X activates also the other β2 integrin receptor, LFA-1 (CD11a/CD18) which is involved in the proliferation of T lymphocytes. By modulating the activity of LFA-1 cathepsin X causes cytoskeletal rearrangements and morphological changes of T lymphocytes enhancing ameboid-like migration in 2-D and 3-D barriers and increasing homotypic aggregation. The cleavage of C-terminal amino acids of α and γ enolase by cathepsin X abolishes their neurotrophic activity affecting neuronal cell survival and neuritogenesis.

10.4161/cam.3.2.7403

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Dušan Pirjevec: (1921–1977)

Slavistična revija/Slavistična revija (1978)

Janko Kos

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Cathepsin X inhibitor decrease the production of cytokines and monocyte microparticles on THP-1 macrophage-like cells stimulated with Helicobacter pylori

Frontiers in Immunology (2013)

Andreja Nataša Kopitar Janko Kos Samo Jeverica Alojz Ihan

Event Abstract Back to Event Cathepsin X inhibitor decrease the production of cytokines and monocyte microparticles on THP-1 macrophage-like cells stimulated with Helicobacter pylori Andreja Natasa Kopitar1*, Janko Kos2, Samo Jeverica1 and Alojz Ihan1 1 University of Ljubljana, Medical Faculty Ljubljana, Institute of Microbiology and Immunology, Immunology, Slovenia 2 University of Ljubljana, Faculty of Pharmacy, Pharmaceutical Biology, Slovenia INTRODUCTON> The infection with Helicobacter pylori (H. pylori) induces higher levels of cathepsin X in macrophages of the gastric mucosa. Cathepsin X has been predominantly localized on monocytes, macrophages and dendritic cells. Active cathepsin X has been shown to regulate β-2 integrin-dependent adhesion and phagocytosis, which is crucial for effective antigen presentation and initiation of T cell dependent immune response. In our opinion inhibition of cathepsin X blocks this process, because the membrane in the case of inhibition becomes more rigid and internalization is delayed or even impossible. Microparticles have been considered as cellular debris for a long time. However recent findings associate them with cellular stimulation, activation, and degeneration/apoptosis. HYPOTHESIS> Our hypothesis suggests that cathepsin X inhibitor could suppress fluidity of plasmatic membrane and microvesiculation of antigen presenting cells. This process could result in the insufficient immune response to the infection with H. pylori. METHODES>Macrophages like cells were differentiated from THP-1 cell line treated with PHA for 24h. The cells were than stimulated with H. pylori strains, isolated from 20 dyspeptic patients. For negative control we used THP-1 cells co-cultivated with medium alone or we added an inhibitor of cathepsin X. The in vitro secretion of IL-1b, IL-6, IL-8, IL-10, IL-12, TNF and concentration of microparticles were measured with flow cytometry. RESULTATES> Higher concentration of microparticles were observed in the cases of THP-1 macrophage like cells, which were treated with H. pylori alone than in the cases of the untreated cells (p<0.01). The amount of microparticles was still significantly higher in the cases of THP-1 cells stimulated with H. pylori in combination with cathepsin X inhibitor as in the cases of un-stimulated THP-1 cells. Cathepsin X inhibitor decreased the amount of microparticles compared to THP-1 cells stimulated with H. pylori alone (p<0.01). The H. pylori stimulation alone as well as the stimulation in combination of cathepsin X inhibitor increased the production of IL-8, IL-6, IL-10, TNF, IL-12 compared to the negative control. However, we observed lower production of IL-1β and IL-6 by the THP-1 cells stimulated with H. pylori in combination with cathepsin X inhibitor (p<0.01). Figure 1 Figure 2 References 1.Kos J, Jevnikar Z, Obermajer N. The role of cathepsin X in cell signaling. Cell adhesion & migration 2009,3:164-166. 2.Kopitar AN, Stegel V, Tepes B, Gubina M, Novakovic S, Ihan A. Specific T cell responses to Helicobacter pylori predict successful eradication therapy. The Journal of infection 2007,54:257-261. 3.Wang JG, Williams JC, Davis BK, Jacobson K, Doerschuk CM, Ting JP, Mackman N. Monocytic microparticles activate endothelial cells in an IL-1β-dependent manner. Blood. 2011 Aug 25;118(8):2366-74. 4.Obermajer N, Magister S, Kopitar AN, Tepes B, Ihan A, Kos J. Cathepsin X prevents an effective immune response against Helicobacter pylori infection. European journal of cell biology 2009,88:461-471. 5.Bernimoulin M, Waters EK, Foy M, Steele BM, Sullivan M, Falet H, Walsh MT, Barteneva N, Geng JG, Hartwig JH, Maguire PB, Wagner DD. Differential stimulation of monocytic cells results in distinct populations of microparticles. J Thromb Haemost. 2009 Jun; 7(6):1019-28. Keywords: H. pylori, Cathepsin X, microparticles, THP-1 macrophages, IL-6, IL-1beta Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Innate immunity Citation: Kopitar A, Kos J, Jeverica S and Ihan A (2013). Cathepsin X inhibitor decrease the production of cytokines and monocyte microparticles on THP-1 macrophage-like cells stimulated with Helicobacter pylori. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.01049 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 30 Jun 2013; Published Online: 22 Aug 2013. * Correspondence: Dr. Andreja Natasa Kopitar, University of Ljubljana, Medical Faculty Ljubljana, Institute of Microbiology and Immunology, Immunology, Ljubljana, SI-1000, Slovenia, andreja-natasa.kopitar@mf.uni-lj.si Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Andreja Natasa Kopitar Janko Kos Samo Jeverica Alojz Ihan Google Andreja Natasa Kopitar Janko Kos Samo Jeverica Alojz Ihan Google Scholar Andreja Natasa Kopitar Janko Kos Samo Jeverica Alojz Ihan PubMed Andreja Natasa Kopitar Janko Kos Samo Jeverica Alojz Ihan Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

THP1 cell line

Monocyte

10.3389/conf.fimmu.2013.02.01049

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Relationship of high circulating cystatin c to biochemical markers of bone turnover and bone mineral density in elderly males with a chronic heart failure

DOAJ (DOAJ: Directory of Open Access Journals) (2019)

Božić-Nedeljković Biljana Lončar Goran Vizin Tjaša Radojičić Zoran Popović-Brkić Vera

Bone remodeling

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CCDC 1997101: Experimental Crystal Structure Determination

The Cambridge Structural Database (2020)

Tim Van de Walle Marina Briand Ana Mitrović Izidor Sosič Stanislav Gobec

10.5517/ccdc.csd.cc2514m0

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Nanoscale polymer carriers to deliver chemotherapeutic agents to tumours

Expert Opinion on Biological Therapy (2005)

Mateja Cegnar Julijana Kristl Janko Kos

Nanoscale polymer carriers have the potential to enhance the therapeutic efficacy of antitumour drugs as they can regulate their release, improve their stability and prolong circulation time by protecting the drug from elimination by phagocytic cells or premature degradation. Moreover, nanoscale polymeric carriers are capable of accumulating in tumour cells and tissues due to enhanced permeability and retention effect or by active targeting bearing ligands designed to recognise overexpressed tumour-associated antigens. The diversity in the polymer structures being studied as drug carriers in cancer therapy allows an optimal solution for a particular drug to be provided regarding its delivery and efficacy, and thus the patient's quality of life. This review is focused on the different types of nanoscale polymer carriers used for the delivery of chemotherapeutic agents and on the factors that affect their cellular uptake and trafficking.

10.1517/14712598.5.12.1557

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L-Amino Acid Oxidases From Mushrooms Show Antibacterial Activity Against the Phytopathogen Ralstonia solanacearum

Frontiers in Microbiology (2020)

Jerica Sabotič Jože Brzin Jana Erjavec T. Dreo Magda Tušek Žnidarič

Ralstonia solanaceraum is the quarantine plant pathogenic bacterium that causes bacterial wilt in over 200 host plants, which include economically important crops such as potato, tomato, tobacco, banana, and ginger. Alternative biological methods of disease control that can be used in integrated pest management are extensively studied. In search of new proteins with antibacterial activity against R. solanacearum, we identified L-amino acid oxidases (LAOs) from fruiting bodies of Amanita phalloides (ApLAO) and Infundibulicybe geotropa (CgLAO). We describe an optimized isolation procedure for their biochemical characterization, and show that they are dimeric proteins with estimated monomer molecular masses of 72 and 66 kDa, respectively, with isoelectric point of pH 6.5. They have broad substrate specificities for hydrophobic and charged amino acids, with highest Km for L-Leu, and broad pH optima at pH 5 and pH 6, respectively. An enzyme with similar properties is also characterized from the mycelia of I. geotropa (CgmycLAO). Fractionated aqueous extracts of 15 species of mushrooms show that LAO activity against L-Leu correlates with antibacterial activity. We confirm that the LAO activities mediate the antibacterial actions of ApLAO, CgLAO, and CgmycLAO. Their antibacterial activities are greater against Gram-negative versus Gram-positive bacteria, with inhibition of growth rate, prolongation of lag-phase, and decreased endpoint biomass. In Gram-positive bacteria, they mainly prolong the lag phase. These in vitro antibacterial activities of CgLAO and CgmycLAO are confirmed in vivo in tomato plants, while ApLAO has no effect on disease progression in planta. Transmission electron microscopy shows morphological changes of R. solanacearum upon LAO treatments. Finally, broad specificity of the antibacterial activities of these purified LAOs were seen for in vitro screening against 14 phytopathogenic bacteria. Therefore, these fungal LAOs show great potential as new biological phytoprotective agents and show the fruiting bodies of higher fungi to be a valuable source of antimicrobials with unique features.

Ralstonia solanacearum

Bacterial wilt

Pathogenic bacteria

10.3389/fmicb.2020.00977

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Maturation of dendritic cells depends on proteolytic cleavage by cathepsin X

Journal of Leukocyte Biology (2008)

Nataša Obermajer Urban Švajger Matthew Bogyo Matjaž Jeras Janko Kos

Abstract The maturation status of dendritic cells (DCs) is crucial for effective antigen presentation and initiation of the primary immune response. Maturation stimuli cause the adhesion of immature DCs to the extracellular matrix, which is accompanied by recruitment of the CD11b/CD18 [macrophage antigen-1 (Mac-1)] integrin receptor, cytoskeleton reorganization, and podosome formation. Cathepsin X, a cysteine protease expressed in DCs and other APCs, is involved in Mac-1 activation. We have shown that during maturation, cathepsin X translocates to the plasma membrane of maturing DCs, enabling Mac-1 activation and consequently, cell adhesion. In mature DCs, cathepsin X redistributes from the membrane to the perinuclear region, which coincides with the de-adhesion of DCs, formation of cell clusters, and acquisition of the mature phenotype. Inhibition of cathepsin X activity during DC differentiation and maturation resulted in an altered phenotype and function of mature DCs. It reduced surface expression of costimulatory molecules, increased expression of inhibitory Ig-like transcripts 3 and 4 (ILT3 and ILT4), almost completely abolished cytokine production, diminished migration, and reduced the capacity of DCs to stimulate T lymphocytes. These results stress the importance of cathepsin X in regulating DC adhesion, a crucial event for their maturation and T cell activation.

10.1189/jlb.0508285

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Multiple splenic abscess in cattle induced by traumatic foreign body penetration from reticulum.

Ozren Smolec Marko Hohšteter Nika Brkljača Bottegaro Berislav Radišić N. Prvanović

Penetration (warfare)

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The influence of macro- and microelements in seminal plasma on diluted boar sperm quality

Acta veterinaria Scandinavica (2017)

Maja Zakošek Pipan Janko Mrkun Breda Jakovac-Strajn Katarina Pavšič Vrtač Janko Kos

Growing evidence indicates that macro- and microelements in the seminal plasma of humans and various domestic animals are of great importance due to their roles in sperm metabolism, function, survival and oxidative stress. In the present study, we therefore determined the concentrations of macro- and microelements in fresh boar seminal plasma and their relation to sperm quality parameters after 3 days of liquid storage was assessed. Twenty ejaculates from eight boars were collected, and semen volume, concentration, sperm motility, morphology, tail membrane integrity, plasma membrane permeability, mitochondrial membrane potential and DNA fragmentation were determined on the day of collection (day 0) and day 3 (72 h) of storage at 15-17 °C. Seminal plasma was separated and the concentrations of macroelements (Na, K, Ca, and Mg) and microelements (Cu, Fe, Zn and Se) were determined.After 3 days of storage Se levels correlated significantly with sperm motility, progressive motility and morphology, all of which are routinely used for semen evaluation. On day 3, Se levels also correlated with tail membrane integrity, viability and intact DNA (P < 0.05). The correlation coefficients showed that mitochondrial function was better preserved at higher levels of Zn, while higher levels of Cu decreased mitochondrial function, but led to the better preservation of DNA. It was also evident that higher levels of Fe were associated with higher proportions of live spermatozoa and of spermatozoa with normal morphology after 3 days of storage (P < 0.05), while higher levels of Ca and Mg in fresh seminal plasma were associated with lower percentages of progressive motile spermatozoa and with a decreased proportion of spermatozoa with intact DNA (P < 0.05). Multivariate analysis including microelements showed that Se significantly affected sperm quality parameters, mentioned above, after 3 days of storage.Macro- and microelements were associated with boar sperm quality and may be important biomarkers of boar sperm quality after liquid storage. Our results demonstrate that the evaluation of Se in fresh boar seminal plasma can serve as an additional tool in predicting sperm quality after storage.

BOAR

Sperm Quality

10.1186/s13028-017-0279-y

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Citations (30)