1. Bronchopulmonary dysplasia and innate immunity : a narrative review of the roles of IL-1β and IL-8 (CXCL8)Dubravka Bačaj Ivanić, Štefan Grosek, Andreja Nataša Kopitar, 2026, pregledni znanstveni članek Povzetek: Background: Bronchopulmonary dysplasia (BPD) is a leading chronic lung complication in extremely premature newborns. The etiological factors contributing to of BPD include both prenatal and postnatal risk factors, as well as activation of innate immunity. Innate immunity and its bioactive mediators play a central role in orchestrating the inflammatory response. Among these, interleukin-1β (IL-1 β) and IL-8 (CXCL8) are particularly prominent. Methods: A structured literature search was conducted across major biomedical databases (PubMed, Scopus, Web of Science, and Ovid MEDLINE) to identify relevant studies published between 1993 and November 2025. Article selection was guided by predefined inclusion criteria focusing on studies that examined IL-1β and IL-8 (CXCL8) in relation to bronchopulmonary dysplasia. Evidence from both human and animal studies was narratively synthesized. Results: This review provides a detailed description of the role of the innate immune system in BPD, including mechanisms of inflammatory initiation, evidence from human and animal studies on IL-1β and IL-8 (CXCL8), and the interaction between these two cytokines in the development of chronic lung disease. Conclusions: Both human and animal studies generally suggest that elevated levels of IL-1β and IL-8 (CXCL8) are closely associated with the development of bronchopulmonary dysplasia in premature infants. Ključne besede: premature infant, chronic lung disease, inflammation, cytokines, chemokines Objavljeno v DiRROS: 22.07.2026; Ogledov: 253; Prenosov: 147
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2. Chemokine CCL5 overexpression combined with radiotherapy modulates Th1-mediated immune response and leads to significant tumor growth delay in mouse tumor modelsTim Božič, Iva Šantek, Živa Pišljar, Simona Kranjc Brezar, Gregor Serša, Boštjan Markelc, Maja Čemažar, 2026, izvirni znanstveni članek Povzetek: This study investigated the antitumor efficacy of chemokine CCL5 gene therapy using gene electrotransfer (GET) in combination with radiotherapy (RT) in solid murine tumors CT26 and 4T1. In vitro, CT26 and 4T1 tumor cells transfected with plasmid DNA (pDNA) encoding CCL5 induced migration of RAW264.7 macrophages. In vivo, CCL5 overexpression achieved via GET of pDNA encoding CCL5 led to increased splenocyte infiltration in dorsal window chamber models. When combined with RT, GET of pDNA encoding CCL5 shifted the tumor cytokine profile toward a proinflammatory state, with elevated Ifn-γ, Cxcl9, Cxcl10, and Il-12α. Although CD8 + and CD4 + T cells were reduced post-treatment, due to radiation-induced cell death, the combination of GET of pDNA encoding CCL5 and RT significantly delayed tumor growth in both models. In 4T1 tumors, this delay was also significant compared to the equivalent treatment with GET of control pDNA. These findings support GET of pDNA encoding CCL5 combined with RT as a strategy to enhance immune-mediated tumor control. Ključne besede: chemokines, gene electrotransfer, gene therapy, mouse, radiotherapy Objavljeno v DiRROS: 13.02.2026; Ogledov: 691; Prenosov: 267
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3. The role of cytokines and chemokines as biomarkers of disease activity in idiopathic nephrotic syndrome in childrenMatjaž Kopač, Aleš Jerin, Agnese Petrera, Joško Osredkar, 2025, izvirni znanstveni članek Povzetek: This study investigates the association of plasma concentrations of various cytokines and chemokines with the disease activity of idiopathic nephrotic syndrome (INS) in children in Slovenia. (2) In a prospective single-center study lasting 18 months, we took sequential plasma samples from children with INS at disease onset or relapse (prior to corticosteroid (CS) therapy), at remission, and after discontinuation of CS therapy. The Olink®Target 48 Cytokine Panel was applied to analyze 45 analytes in the plasma samples, adhering to the manufacturer’s protocol. We performed a statistical analysis with a paired samples analysis with a t-test as well as with a non-parametric Wilcoxon correction test. (3) We included 18 pediatric patients with INS in the study. We demonstrated statistically significant differences in the concentrations of CSF1, IL4, FLT3LG, CCL19, and MMP12 in the patients at disease onset or relapse compared to those in remission, differences in the concentrations of CSF1 and IL17F in the patients at disease onset or relapse compared to those in remission after CS treatment, and differences in the concentrations of CCL19, MMP12, and CCL13 in the patients in remission compared to those in remission after CS treatment. (4) The findings support potential roles of certain cytokines and chemokines, especially CSF1, CCL19, and MMP12, in influencing the disease activity of INS. Ključne besede: cytokines, chemokines, idiopathic nephrotic syndrome, children Objavljeno v DiRROS: 12.02.2026; Ogledov: 686; Prenosov: 289
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4. Cytokine profiles of bronchoalveolar lavage in patients with interstitial lung diseases and non-allergic asthmaDana Greif Lenarčič, Urška Bidovec, Pia Kristanc, Peter Kopač, Mateja Marc-Malovrh, Izidor Kern, Katarina Osolnik, 2025, izvirni znanstveni članek Povzetek: Diagnosing and prognosing immune-mediated airway diseases, like hypersensitivity pneumonitis (HP) and sarcoidosis, is complicated due to their overlapping symptoms and the lack of definitive biomarkers. Hence, we wanted to compare bronchoalveolar lavage (BAL) cytokine and chemokine profiles from 92 patients with different immune-mediated and inflammatory airway diseases, namely, HP, sarcoidosis, non-allergic asthma, amiodarone lung, and EGPA. We also compared pulmonary function parameters, BAL’s cellularity, and lymphocyte immunophenotypes. We found significant differences across all measured lung functions (VC, VC%, FEV1, FEV1%, and Tiff%) and in the number of macrophages, lymphocytes, neutrophils, and eosinophils. Furthermore, we showed significant differences in CD4, CD8, and CD4/8 across all included ILDs and OLDs; however, no significant differences were found in CD3, CD19, NK, or NKT. We identified nine biomarkers (IL-1β, IL-6, IL-8, IL-13, VEGF, angiogenin, C4a, RANTES, and MCP-1) that significantly differ in the BAL of patients with HP and sarcoidosis and showed that RANTES and IL-6 are associated with fibrotic outcome. We have demonstrated that interstitial and obstructive lung diseases differ in cytokine and cellular lung imprint, which may, in the future, enable the determination of the disease subtype and thus the identification of targets for the treatment of individuals or subgroups within diseases. Ključne besede: hypersensitivity pneumonitis, sarcoidosis, non-allergic asthma, amiodarone lung, EGPA, cytokines, bronchoalveolar lavage, chemokines, complement anaphylatoxins, angiogenesis-related factors Objavljeno v DiRROS: 05.08.2025; Ogledov: 1024; Prenosov: 597
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5. CCR5-mediated signaling is involved in invasion of glioblastoma cells in its microenvironmentMetka Novak, Miha Koprivnikar Krajnc, Barbara Hrastar, Barbara Breznik Vittori, Bernarda Majc, Mateja Mlinar, Ana Rotter, Andrej Porčnik, Jernej Mlakar, Katja Stare, Richard G. Pestell, Tamara Lah Turnšek, 2020, izvirni znanstveni članek Povzetek: Abstract
The chemokine CCL5/RANTES is a versatile inflammatory mediator, which interacts with the receptor CCR5, promoting cancer cell interactions within the tumor microenvironment. Glioblastoma is a highly invasive tumor, in which CCL5 expression correlates with shorter patient survival. Using immunohistochemistry, we identified CCL5 and CCR5 in a series of glioblastoma samples and cells, including glioblastoma stem cells. CCL5 and CCR5 gene expression were significantly higher in a cohort of 38 glioblastoma samples, compared to low-grade glioma and non-cancerous tissues. The in vitro invasion of patients-derived primary glioblastoma cells and glioblastoma stem cells was dependent on CCL5-induced CCR5 signaling and is strongly inhibited by the small molecule CCR5 antagonist maraviroc. Invasion of these cells, which was enhanced when co-cultured with mesenchymal stem cells (MSCs), was inhibited by maraviroc, suggesting that MSCs release CCR5 ligands. In support of this model, we detected CCL5 and CCR5 in MSC monocultures and glioblastoma-associated MSC in tissue sections. We also found CCR5 expressing macrophages were in close proximity to glioblastoma cells. In conclusion, autocrine and paracrine cross-talk in glioblastoma and, in particular, glioblastoma stem cells with its stromal microenvironment, involves CCR5 and CCL5, contributing to glioblastoma invasion, suggesting the CCL5/CCR5 axis as a potential therapeutic target that can be targeted with repositioned drug maraviroc. Ključne besede: CCL5, CCR5, chemokines, glioblastoma, invasion, maraviroc, mesenchymal stem cells Objavljeno v DiRROS: 22.07.2024; Ogledov: 1910; Prenosov: 655
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6. Gene electrotransfer of proinflammatory chemokines CCL5 and CCL17 as a novel approach of modifying cytokine expression profile in the tumor microenvironmentTim Božič, Gregor Serša, Simona Kranjc Brezar, Maja Čemažar, Boštjan Markelc, 2021, izvirni znanstveni članek Povzetek: The effectiveness of immunotherapy highly correlates with the degree and the type of infiltrated immune cells in the tumor tissue. Treatments based on modifying the immune cell infiltrate of the tumor microenvironment are thus gaining momentum. Therefore, the aim of our study was to investigate the effects of gene therapy with two proinflammatory chemokines CCL5 and CCL17 on inflammatory cytokine expression profile and immune cell infiltrate in two murine breast tumor models, 4T1 and E0771, and two murine colon tumor models, CT26 and MC38. In vitro, lipofection of plasmid DNA encoding CCL5 or CCL17 resulted in changes in the cytokine expression profile similar to control plasmid DNA, implying that the main driver of these changes was the entry of foreign DNA into the cell%s cytosol. In vivo, gene electrotransfer resulted in high expression levels of both Ccl5 and Ccl17 transgenes in the 4T1 and CT26 tumor models. Besides a minor increase in the survival of the treated mice, the therapy also resulted in increased expression of Cxcl9 and Ifn%, potent activators of the immune system, in CT26 tumors. However, this was not recapitulated in changes of TME, implying that a further refinement of the dosing schedule is needed. Ključne besede: chemokines, cytokine expression, gene electrotransfer, CCL5 Objavljeno v DiRROS: 19.09.2022; Ogledov: 2827; Prenosov: 813
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7. Chemokines during anaphylaxis : the importance of CCL2 and CCL2-dependent chemotactic activity for basophilsRomana Vantur, Maruša Rihar, Ana Koren, Matija Rijavec, Peter Kopač, Urška Bidovec, Renato Eržen, Peter Korošec, 2020, izvirni znanstveni članek Povzetek: Background: The role of chemokines in anaphylaxis is unclear. Methods: We prospectively recruited 49 patients presenting to the emergency department with an acute episode of anaphylaxis and 28 healthy subjects. We measured serum levels of the chemokines CCL2, CCL5, CCL7, CCL8, CCL11, CCL13, CCL17, CCL21, CCL22, CCL24, and CCL26, tryptase, the absolute number of circulating basophils, monocytes, lymphocytes, and PMNs, and whole blood FCER1A, CPA3 and HDC gene expression at two time points: during the anaphylactic episode and in convalescent samples collected approximately 3 months later. We then investigated the in vitro chemotactic activity of chemokines induced during anaphylaxis for the in vitro migration of the corresponding cells. Results: Only CCL2 chemokine levels were signifcantly increased in anaphylaxis samples (median 514 pg/ml) compared to convalescent samples (284 pg/ml, P<0.0001) and healthy subjects (279 pg/ml, P<0.0001); there was no signifcant diference in any of the other chemokines. There was a signifcant positive correlation between the rates of increase of serum CCL2 (median [range]: 106.0% [-44.7% to 557.4%]) and tryptase (133.8% [-6.6% to 893.4%]; r=0.68, P<0.0001) and between the acute concentration of serum CCL2 and the acute concentration of serum tryptase (r=0.77, P<0.0001). The number of circulating basophils, but not other blood cells, signifcantly decreased during anaphylaxis (median 5.0 vs. 19.1 cells/[micro]l in convalescent samples; P<0.0001); a decrease in whole-blood gene expression of basophil markers (P=0.0018) confirmed these changes. Anaphylactic serum enhances the in vitro migration of basophils via CCL2-dependent chemotactic activity; in contrast, no CCL2-dependent chemotactic activity was observed for convalescent samples. Conclusions: Our findings imply an important and specifc role for CCL2-mediated chemotactic activity in the pathophysiology of human anaphylaxis. Ključne besede: anaphylaxis, chemokines, tryptases, basophils, chemotaxis, CCL2, cell migration Objavljeno v DiRROS: 18.01.2021; Ogledov: 4086; Prenosov: 1314
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