Tao Jiang, Shuangjie Li, Lian Tang, Yanfang Tan, Wenxian Ouyang
{"title":"Interleukin 17A promotes glycolysis to activate human hepatic stellate cells by mediating the TRAF2/TRAF5/HuR/PFKFB3 axis.","authors":"Tao Jiang, Shuangjie Li, Lian Tang, Yanfang Tan, Wenxian Ouyang","doi":"10.5114/ceji.2024.145013","DOIUrl":"10.5114/ceji.2024.145013","url":null,"abstract":"<p><strong>Introduction: </strong>Biliary atresia (BA) is an obliterating fibrous inflammatory bile duct disease in infants. Interleukin 17A (IL-17A) is abnormally expressed in patients with BA; however, the mechanism of its expression is unclear.</p><p><strong>Material and methods: </strong>Liver tissues from patients with BA and those with anicteric choledochal cysts (non-BA) were collected. The expression of genes and proteins was determined using RT-qPCR and western blot. Cell biological activities, including viability and proliferation, were evaluated by Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2 <i>'</i>-deoxyuridine (EdU) assay. Glucose uptake and lactate and ATP levels were examined using commercial kits. The extracellular acidification rate (ECAR) level was evaluated by the XF96 Extracellular Flux analyzer. The interactions among TRAF2, TRAF5, and human antigen R (HuR) were validated using co-immunoprecipitation (Co-IP), RNA immunoprecipitation (RIP), and RNA pull-down.</p><p><strong>Results: </strong>In BA patients, IL-17A, TRAF2, TRAF5, and PFKFB3 were highly expressed, and IL-17A expression was positively correlated with PFKFB3, TRAF2, and TRAF5 expression, respectively. IL-17A elevated PFKFB3 expression and promoted glycolysis and the proliferation and fibrosis of hepatic stellate cells (HSCs), which were abolished by 2-deoxy-D-glucose (2-DG) and PFKFB3/TRAF2/TRAF5 silencing. Mechanistically, IL-17A promoted the interactions among HuR, TRAF2 and TRAF5 to form the TRAF2/TRAF5/HuR complex, thereby enhancing PFKFB3 expression.</p><p><strong>Conclusions: </strong>IL-17A facilitates glycolysis and HSC fibrosis by promoting TRAF2/TRAF5/HuR complex formation to regulate PFKFB3 expression.</p>","PeriodicalId":9694,"journal":{"name":"Central European Journal of Immunology","volume":"49 4","pages":"404-424"},"PeriodicalIF":1.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11811719/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143406091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"LncRNA DLEU1 contributes to the progression of septic myocardial dysfunction by targeting miR-381-3p.","authors":"Tian Tian, Na Zhang, Guoxin Hu, Rong Lu, Jian Liu","doi":"10.5114/ceji.2024.144199","DOIUrl":"10.5114/ceji.2024.144199","url":null,"abstract":"<p><strong>Introduction: </strong>Cardiac dysfunction is a common complication of sepsis. This study aimed to elucidate the regulatory effect of DLEU1 on sepsis-induced myocardial injury.</p><p><strong>Material and methods: </strong>HL-1 cardiomyocytes were treated with lipopolysaccharide (LPS) to mimic sepsis-induced myocardial injury in vitro, and the mouse septic model was established through cecum ligation and perforation (CLP). Cell viability was evaluated using Cell Counting Kit-8 (CCK-8), while apoptosis was assessed via Annexin-V staining. Pro-inflammatory factors including tumor necrosis factor <i>α</i> (TNF-<i>α</i>), interleukin (IL)-1 <i>β</i>, IL-6, and oxidative stress indicators were detected by ELISA kits. Cardiac function in mice was determined using cardiac ultrasound, and myocardial indices were detected by ELISA.</p><p><strong>Results: </strong>DLEU1 levels were up-regulated gradually in HL-1 cardiomyocytes after LPS treatment in a dose-dependent manner, along with the overactivation of inflammatory responses and oxidative stress. DLEU1 downregulation alleviated LPS-induced cell apoptosis, inflammatory response and oxidative stress. In vivo, DLEU1 knockdown improved the cardiac function of septic mice, and alleviated inflammation and oxidative stress. MiR-381-3p, acting as a competing endogenous RNA (ceRNA) of DLEU1, reversed the effects of DLEU1 in both septic cell and mouse models.</p><p><strong>Conclusions: </strong>The results indicate that the DLEU1/miR-381-3p axis is an intrinsic regulator of myocardial injury in sepsis.</p>","PeriodicalId":9694,"journal":{"name":"Central European Journal of Immunology","volume":"49 3","pages":"227-237"},"PeriodicalIF":1.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11664811/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142885015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"New T-lymphocyte subpopulations and their characteristics: Challenges to the classical division of lymphocyte function.","authors":"Filip Lewandowski, Paulina Niedźwiedzka-Rystwej","doi":"10.5114/ceji.2024.144071","DOIUrl":"10.5114/ceji.2024.144071","url":null,"abstract":"<p><p>Recent advances in immunology have challenged the conventional division of T-lymphocyte function by uncovering novel subpopulations with diverse roles and characteristics. This article reviews these discoveries and their implications for understanding immune regulation and disease pathogenesis. Innovative techniques have enabled the identification of previously unrecognized T-lymphocyte subsets, disrupting the classical classification system. Helper lymphocytes, including T<sub>fh1</sub>, T<sub>fh2</sub>, T<sub>fh17</sub>, GC-T<sub>fh</sub>, and circulating T<sub>fh</sub> cells, exhibit distinct functions in immune responses and disease states. Additionally, newly identified cytotoxic T-cell subsets, such as CD8<sup>+</sup>CD39<sup>+</sup> and CD8<sup>+</sup>CD28<sup>+</sup> cells, demonstrate unique effector properties with potential therapeutic applications in cancer immunothe- rapy. Furthermore, the discovery of CD20<sup>+</sup> T cells challenges traditional views, offering new avenues for immunotherapy in cancer, autoimmune disorders, and infectious diseases. These findings expand our understanding of T-lymphocyte biology and suggest targets for more effective therapeutic interventions. Further research is essential to fully elucidate the clinical relevance and therapeutic potential of these T-lymphocyte subpopulations, paving the way for personalized and targeted immune-based treatments.</p>","PeriodicalId":9694,"journal":{"name":"Central European Journal of Immunology","volume":"49 3","pages":"308-314"},"PeriodicalIF":1.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11664807/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142885034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bartosz Hanczaruk, Aleksandra Roszko, Kamil Kamiński, Marlena Tynecka
{"title":"Differential diagnosis of eosinophilic oesophagitis variants and biomarker identification: current progress.","authors":"Bartosz Hanczaruk, Aleksandra Roszko, Kamil Kamiński, Marlena Tynecka","doi":"10.5114/ceji.2024.143996","DOIUrl":"10.5114/ceji.2024.143996","url":null,"abstract":"<p><p>Eosinophilic oesophagitis (EoE) is a disease characterized by dysregulated type 2 (T2) immune responses with enormous eosinophilic infiltration restricted to the oesophagus. Currently, the gold standard for EoE diagnosis involves identification of oesophageal dysfunction symptoms followed by the detection of at least 15 infiltrating eosinophils per high-power field in the oesophagus. Unfortunately, achieving 90% sensitivity in EoE histology-based diagnosis requires 5-6 biopsy samples to be collected from both the distal and proximal oesophagus, hindering precise diagnosis in routine clinical practice. Therefore, the development of novel diagnostic approaches differentiating EoE from other EoE-like diseases as well as identifying active and non-active forms of EoE is required. In line with the previously advanced EoE diagnostic panel (EDP), in a recent paper published in Gut (BMJ Journals), Gueguen et al. introduced a Histologically Active EoE Diagnostic Panel (HAEDP) effectively distinguishing patients with the active form of the disease from remission regardless of the fibrosis status and biopsy site. Here, we summarize recent findings and achievements in the development of the differential diagnosis of EoE based on the identification of unique deregulation in gene expression.</p>","PeriodicalId":9694,"journal":{"name":"Central European Journal of Immunology","volume":"49 4","pages":"438-441"},"PeriodicalIF":1.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11811723/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143406089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yanan Zhao, Di Wu, Quanjun Yao, Hang Yuan, Hongtao Hu, Hailiang Li
{"title":"Progression patterns in patients with advanced hepatocellular carcinoma treated with local therapy, targeted drugs, and PD-1/PD-L1 inhibitors.","authors":"Yanan Zhao, Di Wu, Quanjun Yao, Hang Yuan, Hongtao Hu, Hailiang Li","doi":"10.5114/ceji.2024.142418","DOIUrl":"https://doi.org/10.5114/ceji.2024.142418","url":null,"abstract":"<p><strong>Introduction: </strong>To explore the progression patterns of advanced hepatocellular carcinoma (HCC) in patients treated with a combination of local therapies, targeted drugs, and PD-1/PD-L1 inhibitors.</p><p><strong>Material and methods: </strong>A retrospective study involving 86 patients with Barcelona Clinic Liver Cancer stage C HCC was conducted between August 2018 and April 2022. All patients received local therapy, targeted drugs, and PD-1/PD-L1 inhibitors. Disease progression was evaluated using computed tomography or magnetic resonance imaging after combination therapy. Peripheral blood immune cells were analyzed using flow cytometry.</p><p><strong>Results: </strong>For intrahepatic progression, the median time to first progression was 5.3 months in 60 patients (95% confidence interval (CI): 2.3-7.1 months), and the median time to second progression was 9.3 months in 40 patients (95% CI: 4.8-11.8 months, p < 0.0001). For extrahepatic progression, the median time to first progression was 5.8 months in 61 patients (95% CI: 1.6-8.4 months), and the median time to second progression was 8.7 months in 39 patients (95% CI: 4.5-10.9 months, p < 0.0001). The common sites of extrahepatic progression are the lymph nodes and lungs. The percentages of PD-1+ cells gradually decreased after combination treatment but then gradually increased at follow-up in extrahepatic progression. The percentages of CD3+ T cells, CD3+CD4+ T cells, CD3+CD8+ T cells and CD16+CD56+ cells exhibited different trends in intrahepatic and extrahepatic progression.</p><p><strong>Conclusions: </strong>After combination treatment, patients with advanced HCC exhibit different characteristics of disease progression and composition of peripheral blood immune cells. Lymph nodes and lungs were the most susceptible sites for disease progression.</p>","PeriodicalId":9694,"journal":{"name":"Central European Journal of Immunology","volume":"49 2","pages":"147-154"},"PeriodicalIF":1.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11457562/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Agata Poniewierska-Baran, Jacek Tabarkiewicz, Urszula Radzikowska, Marlena Tynecka, Andrzej Eljaszewicz
{"title":"The pivotal role of IL-17A in hepatic stellate cell activation.","authors":"Agata Poniewierska-Baran, Jacek Tabarkiewicz, Urszula Radzikowska, Marlena Tynecka, Andrzej Eljaszewicz","doi":"10.5114/ceji.2024.146900","DOIUrl":"10.5114/ceji.2024.146900","url":null,"abstract":"","PeriodicalId":9694,"journal":{"name":"Central European Journal of Immunology","volume":"49 4","pages":"331"},"PeriodicalIF":1.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11811722/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143406077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"High mobility group box protein 1 sensitizes mononuclear cells to further contact with lipopolysaccharide.","authors":"Jakub Piotrowski, Tomasz Jędrzejewski","doi":"10.5114/ceji.2024.138600","DOIUrl":"10.5114/ceji.2024.138600","url":null,"abstract":"<p><p>Fever is an adaptive host-defense response to infection and nowadays is rightly considered to be an expression of a healthy body and a well-functioning immune system. The condition is that it must be tightly regulated. Therefore, in individual cases, fever may be detrimental and should be treated. Specific excessive febrile reaction to pathogens which occurs after aseptic injuries is one among such cases. We previously found that among necrotic products, high mobility group box protein 1 (HMGB1) released from the site of aseptic injury affects immune effectors (cells) to mediate higher fever in response to further contact with bacterial lipopolysaccharide (LPS). Here we observed that intraperitoneal (i.p.) pre-injection of recombinant HMGB1 (5 µg/rat i.p.) provoked an increase in plasma levels of prostaglandin E2 (PGE2) in rats and augmented release of interleukin (IL)-1β and IL-6 after LPS administration at a dose of 50 µg/kg i.p. compared to rats pre-injected with saline or heat-denatured HMGB1. Furthermore, peripheral blood mononuclear cells (PBMCs) isolated from rats injected with HMGB1 were more sensitized to produce enhanced levels of IL-1β and PGE2 when stimulated with LPS in vitro (1 µg/ml/10<sup>6</sup> cells for 4 h) compared to control animals injected with saline or heat-denatured HMGB1. We also noted a significant increase in activation of nuclear factor κB (NF-κB) in cells isolated from rats injected with HMGB1. Altogether, the obtained results suggest that HMGB1 participates in priming of immune cells to further contact with pathogens.</p>","PeriodicalId":9694,"journal":{"name":"Central European Journal of Immunology","volume":"49 1","pages":"52-59"},"PeriodicalIF":1.3,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11130980/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141175021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Risk factors of thyroid dysfunction in patients with rheumatoid arthritis.","authors":"Lan Li, Fuda Jiao, Jinmei Zhao, Lizhi Duan","doi":"10.5114/ceji.2024.140634","DOIUrl":"https://doi.org/10.5114/ceji.2024.140634","url":null,"abstract":"<p><strong>Introduction: </strong>The study aimed to investigate the complicating thyroid dysfunction situation in patients with rheumatoid arthritis (RA) and to analyze the related risk factors of thyroid dysfunction in RA patients.</p><p><strong>Material and methods: </strong>The retrospective analysis of the clinical data and laboratory examinations of 290 cases of RA and 200 healthy individuals undergoing the physical examination was carried out. The thyroid function, anti-thyroid antibodies, and routine laboratory test items were measured. The RA disease activity score (DAS28) was determined in RA patients. Logistic analysis was used to identify risk factors associated with thyroid dysfunction in RA patients.</p><p><strong>Results: </strong>The detection rate of RA combined with thyroid dysfunction was 30.0%, which was higher than in the control group (7%, 14 cases). In the thyroid function test, levels of total triiodothyronine (T3) and free triiodothyronine (FT3) were lower, while thyrotropin (TSH), antithyroid peroxidase antibody (TPOAb), and antithyroglobulin antibody (TgAb) were higher in the RA group. There was a difference in hemoglobin (HGB) and total cholesterol (TC) in RA patients with and without abnormal thyroid function.</p><p><strong>Conclusions: </strong>Rheumatoid arthritis patients are more prone to develop thyroid dysfunction than healthy individuals, especially hypothyroidism. HGB and TC were correlated with thyroid hormones and antibodies and were risk factors correlated with thyroid dysfunction in RA patients. Clinical work should pay full attention to changes in thyroid function in patients with RA.</p>","PeriodicalId":9694,"journal":{"name":"Central European Journal of Immunology","volume":"49 2","pages":"126-131"},"PeriodicalIF":1.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11457566/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Immune regulation is more effective in the U937 inflammation model with mesenchymal stem cell extracellular vesicles stimulated by pro-inflammatory cytokines.","authors":"Canan Öztürk, Zehra S Halbutoğulları","doi":"10.5114/ceji.2024.143726","DOIUrl":"10.5114/ceji.2024.143726","url":null,"abstract":"<p><p>Mesenchymal stem cells (MSCs), which are multipotent adult cells with many therapeutic effects, can be derived from stromal tissues. MSCs also exert immunoregulatory effects through extracellular vesicles (EVs), cell membrane structures that carry paracrine factors. It is thought that the mediators (cytokines, growth factors, etc.) secreted by stem cells change under inflammatory conditions, and the therapeutic activity of MSCs increases. The purpose of this study was to investigate the possible effects of stimulated human Wharton's jelly-derived mesenchymal stem cell extracellular vesicles, obtained with or without stimulation with inflammatory cytokines, on inflammation. The study aimed to determine the effects of pro-inflammatory cytokines interleukin 1 <i>β</i> (IL-1 <i>β</i>), interferon <i>γ</i> (IFN-<i>γ</i>), and tumor necrosis factor <i>α</i> (TNF-<i>α</i>) stimulated extracellular vesicles (sEVs) on the inflammation model U937 macrophages induced by phorbol-12-myristate 13-acetate (PMA) and lipopolysaccharide (LPS) treatment. Experimental studies were designed to investigate the effects of EVs obtained without stimulation with inflammatory cytokines and those obtained after stimulation with inflammatory cytokines in the macrophage cell line U937. Flow cytometry, gene expression, and immunofluorescence analyses were performed to investigate the apoptotic and antiproliferative effects of EVs and sEVs in the U937 macrophage inflammation model. WJ-MSC EVs obtained after culture with inflammatory cytokines had a greater apoptotic effect on U937 cells and reduced inflammatory cytokine release than EVs cultured in standard medium.</p>","PeriodicalId":9694,"journal":{"name":"Central European Journal of Immunology","volume":"49 3","pages":"282-299"},"PeriodicalIF":1.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11664804/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142885007","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"A case of trigeminal neuralgia that occurred after COVID-19 vaccination.","authors":"Zeliha Ünlü, İlhan Celil Özbek","doi":"10.5114/ceji.2024.142414","DOIUrl":"https://doi.org/10.5114/ceji.2024.142414","url":null,"abstract":"","PeriodicalId":9694,"journal":{"name":"Central European Journal of Immunology","volume":"49 2","pages":"92-93"},"PeriodicalIF":1.5,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11457563/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}