Cytokine最新文献

{"title":"Effects of Fisetin and Nicorandil on adjuvant-induced rheumatoid arthritis in rats: Emerging role of TLR4/NF-κB-induced Pyroptosis, Nrf-2/HO-1, and OPG/RANKL pathways","authors":"Asmaa H. Okasha ,&nbsp;Islam Ibrahim Hegab ,&nbsp;Monira A. Seleem ,&nbsp;Asmaa R. Azzam ,&nbsp;Sarah Ibrahim ,&nbsp;Asmaa A. Ghalwash ,&nbsp;Rehab M. El-Gohary","doi":"10.1016/j.cyto.2025.156876","DOIUrl":"10.1016/j.cyto.2025.156876","url":null,"abstract":"<div><h3>Aim and <strong>background</strong></h3><div>Our study explored the novel mechanisms implicated in the anti-rheumatic potential of fisetin and/or nicorandil (NIC) intervention.</div></div><div><h3>Methods and Materials:</h3><div>Fifty male rats were categorized into; control, rheumatoid arthritis (RA), fisetin-treated RA, NIC-treated RA, and co-treated RA groups. We assessed paw thickness, arthritis indices, serum CRP, RF, OPG, RANKL, and gene expressions of synovial TLR4, NLRP3, caspase-1, GSDMD, Nrf-2, and HO, along with synovial histopathology and NF-κB immunoreactivity.</div></div><div><h3>Results</h3><div>The combined therapy demonstrated significantly better anti-rheumatic potential, suppressing oxidative stress and NF-κB, downregulating synovial TLR4, NLRP3, caspase-1, GSDMD, and increasing serum OPG while decreasing RANKL, confirmed by histopathological findings.</div></div><div><h3>Conclusion</h3><div>Our investigation uncovered the TLR4/NF-κB pyroptotic signaling, Nrf-2/HO-1, and OPG/RANKL pathways as novel mechanistic insights into the anti-rheumatoid potential of fisetin and/or NIC, with superiority of combination approach, providing a beacon of hope for RA patients in terms of optimizing treatment protocol effectiveness and patient outcomes.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"187 ","pages":"Article 156876"},"PeriodicalIF":3.7,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143062677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immune mechanisms in multiple sclerosis: CD3 levels on CD28+ CD4+ T cells link antibody responses to human herpesvirus 6","authors":"Liang Cao ,&nbsp;Chen Chen ,&nbsp;Wenjun Pi ,&nbsp;Yi Zhang ,&nbsp;Sara Xue ,&nbsp;Voon Wee Yong ,&nbsp;Mengzhou Xue","doi":"10.1016/j.cyto.2025.156866","DOIUrl":"10.1016/j.cyto.2025.156866","url":null,"abstract":"<div><div>Compelling evidence suggests a significant association between antibody-mediated immune responses and multiple sclerosis (MS). However, the exact causal relationships between these immune responses and MS remain unclear. In this study, we conducted a comprehensive examination of the link between antibody-mediated immune responses and MS via Mendelian randomization (MR) analysis to identify specific infectious pathogens potentially involved in the onset and progression of MS. We compared immune cell infiltration between MS patients and control subjects. Furthermore, single-cell sequencing was employed to conduct a comparative analysis of the marker genes associated with each cell subtype between individuals diagnosed with MS and the control cohort. We revealed connections between antibody-mediated immune responses and immune cells, as well as the associations between these immune cells and MS. We discovered that CD3 levels on CD28⁺ CD4⁺ T cells significantly influence MS progression by altering the ratio of human herpesvirus 6 (HHV-6). These findings provide novel insights into the biological mechanisms underlying HHV–6–mediated MS.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"187 ","pages":"Article 156866"},"PeriodicalIF":3.7,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143062681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transforming growth factor beta induces interleukin-11 expression in osteoarthritis","authors":"Juliane Lokau ,&nbsp;Miriam Bollmann ,&nbsp;Yvonne Garbers ,&nbsp;Eugen Feist ,&nbsp;Christoph H. Lohmann ,&nbsp;Jessica Bertrand ,&nbsp;Christoph Garbers","doi":"10.1016/j.cyto.2025.156863","DOIUrl":"10.1016/j.cyto.2025.156863","url":null,"abstract":"<div><div>Interleukin-11 (IL-11) is a member of the IL-6 family of cytokines and possesses both pro- and anti-inflammatory properties. IL-11 activates its target cells via binding to a membrane-bound IL-11R and subsequent formation of a homodimer of the signal-transducing receptor gp130. Thus, the expression pattern of the IL-11R determines which cells can be activated by IL-11. However, knowledge about IL-11 target cells and cells that secrete IL-11 are sparse, and the overall roles of IL-11 in inflammatory diseases are largely unexplored. In this study, we show that high amounts of IL-11 can be detected via ELISA in the synovial fluid of osteoarthritis (OA) patients in comparison to rheumatoid arthritis (RA) patients. Using primary cells and tissue of OA patients, we show that IL-11 is expressed by chondrocytes in cartilage, but not in the synovium. We further identify the cytokine transforming growth factor β 1(TGF-β1) as a potent inducer of IL-11 secretion in both primary chondrocytes and fibroblasts, and TGF-β1 and IL-11 levels correlate significantly in the synovial fluid of OA patients. Using immunohistochemistry, we show that both cartilage and synovium express IL-11R, and the amount of IL-11R is independent of the disease severity. Primary chondrocytes and fibroblasts from OA patients respond to IL-11 stimulation with potent activation of the Jak/STAT3 signaling cascade, suggesting that these cell types are not only the source, but also the targets of IL-11 in OA patients. Our results uncover IL-11 as a potential new target for therapy in OA.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"187 ","pages":"Article 156863"},"PeriodicalIF":3.7,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143062735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TLR3 as an emerging molecule facilitating pyroptosis in the context of rheumatoid arthritis: A study combined bioinformatics and experimental validation","authors":"Meng-yuan Zhou ,&nbsp;Hong-yan Feng ,&nbsp;Tian-tian Wang ,&nbsp;Ze-shan Xu ,&nbsp;Sheng-long Gu ,&nbsp;Ling-ling Li ,&nbsp;Li Cai ,&nbsp;Rong Li","doi":"10.1016/j.cyto.2025.156875","DOIUrl":"10.1016/j.cyto.2025.156875","url":null,"abstract":"<div><h3>Background</h3><div>Rheumatoid arthritis (RA) is an inflammatory disease of the joints mediated by immune cells. As an immune-related mode of cell death, pyroptosis has yet to be fully understood in RA. This research identified novel pyroptosis-related markers in RA and confirmed its functional significance in RA.</div></div><div><h3>Methods</h3><div>Initially, crucial pyroptosis-related genes of RA were identified through GEO database, and biological pathways were determined through enrichment analysis. Then, PPI network, WGCNA and CIBERSORT analysis was utilized to screen hub genes and evaluate immune cell infiltration levels. Finally, validation experiments determined hub genes expression and regulatory roles in RA pathogenesis, and screened potential therapeutic drugs.</div></div><div><h3>Results</h3><div>A total of 46 DEPRGs in RA were identified, which involved in NOD-like receptor and Toll-like receptor signaling pathway. Further screening revealed 3 crucial hub genes: CCL5, LY96, and TLR3 had significantly increased expression in RA synovial tissue and FLS, which might become diagnostic markers of RA. Analysis of immune infiltration revealed that hub genes exhibited associations with plasma cells, T lymphocytes, and macrophages. Further study on the crucial hub gene TLR3 revealed that knocking down TLR3 significantly inhibited the RA FLS hyperproliferation and pyroptosis, and dexamethasone and doxorubicin, as potential drugs, could treat RA by inhibiting TLR3.</div></div><div><h3>Conclusion</h3><div>Our study indicates that high expression of TLR3 promotes FLS pyroptosis and RA progression, suggesting its potential as both a biomarker and a therapeutic target for RA.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"187 ","pages":"Article 156875"},"PeriodicalIF":3.7,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143062733","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Knockout or treatment with an antagonist of formyl peptide receptor 1 protects mice from sepsis by inhibiting inflammation","authors":"Gang Ma ,&nbsp;Jie Ma ,&nbsp;Baofu Qu ,&nbsp;Caixia Zhang ,&nbsp;Jinyuan Zhu ,&nbsp;Yi Chen ,&nbsp;Yujie Ma ,&nbsp;Xiangkun Meng","doi":"10.1016/j.cyto.2025.156872","DOIUrl":"10.1016/j.cyto.2025.156872","url":null,"abstract":"<div><h3>Background</h3><div>Sepsis is an infection-related systemic inflammation with high mortality rates. Activation of formyl peptide receptor 1 (FPR1) in immune cells can promote their chemotaxis and inflammatory response, which imbalances immune response during the process of sepsis. FPR1 blockade did diminish systemic inflammatory response during bacterial infection. Accordingly, this study tested the hypothesis that knockout or treatment with an antagonist of FPR1 could protect animals from sepsis-related death.</div></div><div><h3>Methods</h3><div>Wild-type (WT) or <em>Fpr1</em> gene knockout (<em>Fpr1</em>^−/−) C57BL/6 mice were subjected to the process of cecal ligation and puncture (CLP) to induce different grades of sepsis. Some WT mice were treated with cinnamoylphenylalanine-(D)leucine-phenylalanine-(D)leucine-phenylalanine (cFLFLF), a FPR1 antagonist. Their survival rate was evaluated, their blood and peritoneal flushing samples were collected at 6 and 24 h after the induction of sepsis for biochemical analyses. We also enrolled 143 sepsis patients, their blood and neutrophil samples were collected for analysis of FPR1 expression by RT-qPCR, and their 28-day survival was recorded.</div></div><div><h3>Results</h3><div>All mice died by day 6 after high grade sepsis regardless of <em>Fpr1</em>^−/− or cFLFLF treatment. <em>Fpr1</em> gene knockout or cFLFLF treatment increased the survival rate of mice with a mid-to-low grade of sepsis, accompanied by a significant decrease in the levels of serum and peritoneal inflammatory markers (IL-6, IL-1β and TNF-α). Induction of sepsis increased the percentages of blood neutrophils, and the counts of peritoneal bacterial colony forming units, but decreased body temperature in WT mice, but not in the <em>Fpr1</em>^−/− mice or cFLFLF-treated sepstic mice. Analysis of clinical data indicated that sequential organ failure assessment score and old age were independent risk factors for 28-day mortality.</div></div><div><h3>Conclusion</h3><div><em>Fpr1</em> gene knockout or cFLFLF treatment increased the survival rate of animals with a mid-to-low grade of sepsis, in part by inhibiting abdominal and systemic inflammation during the early period of sepsis. FPR1 protein level in neutrophils was not an independent risk factor of 28-day mortality in sepsis patients.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"187 ","pages":"Article 156872"},"PeriodicalIF":3.7,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143062685","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prognostic significance of cytokine dysregulation in critically ill COVID-19 patients","authors":"Fabian Fellipe Bueno Lemos ,&nbsp;Luana Weber Lopes ,&nbsp;Gabriel Carvalho Brito ,&nbsp;Airton Idalecio Sousa Viana ,&nbsp;Caroline Tianeze de Castro ,&nbsp;Marcel Silva Luz ,&nbsp;André Pereira Gonçalves ,&nbsp;Rafael Santos Dantas Miranda Dórea ,&nbsp;Filipe Antônio França da Silva ,&nbsp;Breno Bittencourt de Brito ,&nbsp;Maria Luísa Cordeiro Santos ,&nbsp;Geovani Moreno Santos Júnior ,&nbsp;Maria Teresa Araújo de Lorenzo Barcia ,&nbsp;Renata de Amorim Marques ,&nbsp;André Bezerra Botelho ,&nbsp;Anna Carolina Saúde Dantas ,&nbsp;Fillipe Dantas Pinheiro ,&nbsp;Adriano Fernandes Teixeira ,&nbsp;Cláudio Lima Souza ,&nbsp;Márcio Vasconcelos Oliveira ,&nbsp;Fabrício Freire de Melo","doi":"10.1016/j.cyto.2025.156867","DOIUrl":"10.1016/j.cyto.2025.156867","url":null,"abstract":"<div><h3>Background</h3><div>Understanding the immunopathogenesis of COVID-19 has yielded valuable insights into predicting adverse outcomes—particularly mortality. However, significant gaps persist in our comprehension of the complex interplay among the proposed pathophysiological mechanisms. Here, we aim to investigate the immunological factors associated with mortality in critically ill, unvaccinated COVID-19 patients admitted to the intensive care unit (ICU).</div></div><div><h3>Methods</h3><div>We conducted a single-center, prospective study involving 56 unvaccinated COVID-19 patients admitted to the ICU. Plasma cytokine levels at admission were quantified using enzyme-linked immunosorbent assay (ELISA). Continuous variables were presented as median (IQR), and categorical variables as frequencies and percentages. Non-parametric tests assessed group differences. Logistic regression and receiver operating characteristic (ROC) curve analyses identified predictors of mortality, with bootstrapping (1000 re-samplings; 95 % BCa CI) applied for model validation.</div></div><div><h3>Results</h3><div>Deceased patients exhibited significantly higher levels of interleukin (IL)-1β, IL-2, IL-6, transforming growth factor (TGF)-β, and interferon (IFN)-γ compared to survivors. Conversely, IL-10 and IL-27 were associated with favorable outcomes. Logistic regression modeling identified elevated IL-2 and IFN-γ levels as significant predictors of mortality. Notably, individual ROC curve analyses demonstrated that IL-1β and TGF-β had excellent discriminatory ability for mortality, while IFN-γ, IL-2, and IL-27 showed very good to excellent discriminatory capacity.</div></div><div><h3>Conclusion</h3><div>Our results indicate that distinct cytokine profiles differentiate survivors from non-survivors in critically ill, unvaccinated COVID-19 patients. These findings highlight the importance of cytokine dysregulation in severe COVID-19 cases and suggest potential targets for prognostic approaches. Further research is warranted to validate these results and translate them into effective clinical management strategies.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"187 ","pages":"Article 156867"},"PeriodicalIF":3.7,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143057643","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TGF-beta plays dual roles in immunity and pathogenesis in leishmaniasis","authors":"Susmita Barik ,&nbsp;Sanghamitra Goswami ,&nbsp;Prakash Kumar Nanda ,&nbsp;Argajit Sarkar ,&nbsp;Bhaskar Saha ,&nbsp;Arup Sarkar ,&nbsp;Surajit Bhattacharjee","doi":"10.1016/j.cyto.2025.156865","DOIUrl":"10.1016/j.cyto.2025.156865","url":null,"abstract":"<div><div>Transforming growth factor-beta (TGF-β), displaying a dual role in immunosuppression and pathogenesis, has emerged as a key regulator of anti-leishmanial immune responses. In <em>Leishmania</em> infections, TGF-β drives immune deviation by enhancing regulatory T-cell (T-reg) differentiation and inhibiting macrophage activation, suppressing critical antiparasitic responses. This cytokine simultaneously promotes fibroblast proliferation, extracellular matrix production, and fibrosis in infected tissues, which aids in wound healing but impedes immune cell infiltration, particularly in visceral leishmaniasis, where splenic disorganization and compromised immune access are notable. In conjunction with IL-6, TGF-β modulates pathogenic Th17 responses which intensify inflammatory damage and disrupt tissue architecture. While TGF-β's immunosuppressive actions enable parasite persistence, its role in maintaining tissue integrity introduces therapeutic potential. Targeted modulation of TGF-β signaling, through selective inhibitors of TGF-β receptors or signaling intermediates, has the potential to enhance parasite clearance while minimizing immunopathology. Experimental studies suggest that phase-specific intervention strategies may allow for controlled immunostimulation or fibrosis reduction, enhancing host resistance without incurring inflammatory injury. This review discusses the intricate role of TGF-β in orchestrating immune deviation, fibrosis, and pathogenesis in leishmaniasis, proposing novel therapeutic avenues for selective modulation of TGF-β pathways to restore host immunity.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"187 ","pages":"Article 156865"},"PeriodicalIF":3.7,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143057644","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association between clinical activity score and serum sPD-1 and sPD-L1 levels during systemic glucocorticoid treatment for active moderate-to-severe thyroid eye disease","authors":"Katarzyna Cieplińska ,&nbsp;Emilia Niedziela ,&nbsp;Agata Kopacz Rdzanek ,&nbsp;Anna Słuszniak ,&nbsp;Magdalena Chrapek ,&nbsp;Iwona Pałyga ,&nbsp;Aldona Kowalska","doi":"10.1016/j.cyto.2025.156862","DOIUrl":"10.1016/j.cyto.2025.156862","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;CD4+ T lymphocytes are key immune cells involved in orbital inflammation in thyroid eye disease (TED). Inhibition of their activity is important in treatment of TED, but effective drugs targeting these cells are lacking. The programmed cell death-1/programmed cell death ligand-1 pathway has been implicated in several T-cell-mediated diseases. Manipulation of this pathway with antagonists or agonists is an attractive therapeutic option. The role of soluble programmed cell death-1 (sPD-1) and soluble programmed cell death ligand-1 (sPD-L1) in regulation of this pathway is debated. This study aimed to investigate the involvement of sPD-1 and sPD-L1 in the pathogenesis of TED, focusing on their utility as novel biomarkers to evaluate disease severity and treatment response.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Thirty patients diagnosed with moderate-to-severe TED associated with Graves' disease were included. Blood samples were collected from patients before and 12 weeks after initiation of intravenous glucocorticosteroid (IVGC) treatment. Disease severity was assessed using the Clinical Activity Score (CAS) before and after IVGC treatment. Thyroid-stimulating hormone, free thyroxine, free triiodothyronine, thyroid-stimulating immunoglobulin, interleukin-6, sPD-1, and sPD-L1 levels were measured. Correlations between sPD-1, sPD-L1, and CAS before and after IVGC treatment were investigated. Serum concentrations of sPD-1 and sPD-L1 before and after IVGC treatment in patients with TED were compared with those in healthy controls (HCs). The changes in the tested protein concentrations upon IVGC treatment and their associations with clinical characteristics were investigated. Enzyme-linked immunosorbent assays were used to measure sPD-1 and sPD-L1 concentrations in peripheral blood serum.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;There was a positive correlation of moderate Spearman's rank strength between sPD-L1 and CAS before and after treatment, and a positive correlation between sPD-1 and sPD-L1. However, no correlation was observed between sPD-1 and CAS. Baseline serum levels of sPD-1 and sPD-L1 did not significantly differ between patients with TED and HCs. There were no correlations between changes in the levels of the tested molecules upon IVGC treatment and the analyzed clinical features. The decreases of sPD-1 and sPD-L1 levels after 12 weeks of IVGC treatment were not significant.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusion&lt;/h3&gt;&lt;div&gt;The positive correlation of moderate Spearman's rank strength between sPD-L1 and CAS before and after 12 weeks of treatment indicates that sPD-L1 is involved in the pathogenesis of TED. sPD-L1 may become an additional immunological biomarker to assess the disease activity and monitor the respond to treatment.&lt;/div&gt;&lt;div&gt;Although sPD-1 is reported in the literature to have an activating effect on lymphocytes, our study shows that sPD-1 may not play a significant role in the pathogenesis of TED, as its level","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"187 ","pages":"Article 156862"},"PeriodicalIF":3.7,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143021433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of basic fibroblast growth factor on hypoxia-inducible factor (HIF)-1α expression (Exp) and HIF-1 transcription in breast Cancer cell through PI-3 K Akt signaling","authors":"Chengcai Zhang ,&nbsp;Jinxia Yu ,&nbsp;Shuaifeng Li","doi":"10.1016/j.cyto.2025.156859","DOIUrl":"10.1016/j.cyto.2025.156859","url":null,"abstract":"<div><h3>Objective</h3><div>To investigate the effect of basic fibroblast growth factor (bFGF) on hypoxia-inducible factor (HIF)-1α expression (Exp) and HIF-1 transcription in breast cancer (BC) cells.</div></div><div><h3>Methods</h3><div>Human BC cell line T47D was utilized as the research object. Western blot and dual-luciferase system were utilized to detect HIF-1α Exp induced by bFGF in BC cells under hypoxia and normal oxygen conditions, as well as the Exp of phosphorylated ERK1/2, Akt, and p38 proteins, HIF-1α Exp induced by bFGF under kinase inhibitors' action, and HIF-1 transcription, thereby summarizing the impact of bFGF on BC cells and its association with PI-3 K Akt signaling pathway (SPW).</div></div><div><h3>Results</h3><div>The maximum Exp fold was 4.9 when the induced dose of bFGF was 10 ng/mL under hypoxia, and the maximum Exp fold of HIF-1α was 7 at 3 h (180 min). Under normal oxygen condition, cycloheximide inhibited HIF-1α protein Exp, and the reduction was up to 50 % within 30 min. Various doses of kinase inhibitor SU5402 inhibited HIF-1α protein Exp, and the inhibition rate was 100 %. The kinase inhibitors SU5402, PD98059, and LY294002 all had marked effects on bFGF-induced HIF-1 transcription.</div></div><div><h3>Conclusion</h3><div>Both MEK1/ERK and PI-3 K/Akt SPW play crucial roles in bFGF-mediated HIF-1 activation. BFGF had a notable activation of HIF-1. PI-3 K/Akt and MEK1/ERK SPW worked together to regulate this process by various mechanisms.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"187 ","pages":"Article 156859"},"PeriodicalIF":3.7,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142997492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Upregulating lncRNA GUSBP11 protects chondrocytes from IL-1β-induced inflammatory damage via inhibiting miR-122-5p","authors":"Zhanqiu Xu ,&nbsp;Peigang Guo ,&nbsp;Lujun Li ,&nbsp;Zhiyuan Li ,&nbsp;Hong Li","doi":"10.1016/j.cyto.2025.156858","DOIUrl":"10.1016/j.cyto.2025.156858","url":null,"abstract":"<div><div>Studies have demonstrated that several lncRNAs exhibit abnormal expression levels in patients suffering from osteoarthritis, and in-depth investigation of these aberrantly expressed lncRNAs may pave the way for innovative therapeutic strategies targeting OA. The aim of this study was to examine the expression of glucuronidase beta pseudogene 11 (GUSBP11) in OA patients and to elucidate its potential molecular mechanism. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was used to detect GUSBP11 levels on cartilage tissues and serum samples obtained from OA patients. To establish an in vitro OA cell model, interleukin-1β (IL-1β) was utilized to induce CHON-001 and ATDC5 cell lines. Cell counting kit-8 (CCK-8) assay and flow cytometry were performed to evaluate cell viability and apoptosis, and enzyme-linked immunosorbent assay (ELISA) was employed to qualify the levels of inflammatory factors. StarBase database predicted that miR-122-5p was the target gene of GUSBP11. Subsequently, luciferase reporter genes were conducted to validate this interaction. Potential target genes of miR-122-5p were predicted, followed by gene function annotation and correlation analysis of these targets. Our findings revealed that GUSBP11 expression was markedly decreased in both the cartilage tissues and serum of OA patients. Diminished levels of GUSBP11 showed high diagnostic accuracy for OA. In the IL-1β-induced OA cell model, GUSBP11 expression was notably reduced, leading to decreased cell viability, an increase in apoptotic cells, and elevated levels of inflammatory factors. Up-regulation of GUSBP11 significantly ameliorated these adverse effects. Luciferase reporter genes confirmed the interaction between GUSBP11 and miR-122-5p, indicating that an increase in miR-122-5p drastically inhibited cell viability while promoting apoptosis and inflammation. In conclusion, within the context of the in vitro OA cell model, GUSBP11 appears to exacerbate IL-1β-induced chondrocyte inflammation through the up-regulation of miR-122-5p. This underscores the potential of GUSBP11 as a novel target and avenue for therapeutic intervention in the treatment of OA.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"187 ","pages":"Article 156858"},"PeriodicalIF":3.7,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142997494","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}