Cytokine最新文献

{"title":"Cytokine atlas of the population-based cohort SHIP-TREND-0 – Associations with age, sex, and BMI","authors":"Sabine Ameling ,&nbsp;Sandra Van der Auwera ,&nbsp;Silva Holtfreter ,&nbsp;Anja Wiechert ,&nbsp;Stephan Michalik ,&nbsp;Nele Friedrich ,&nbsp;Elke Hammer ,&nbsp;Henry Völzke ,&nbsp;Matthias Nauck ,&nbsp;Hans J. Grabe ,&nbsp;Barbara M. Bröker ,&nbsp;Uwe Völker","doi":"10.1016/j.cyto.2025.156896","DOIUrl":"10.1016/j.cyto.2025.156896","url":null,"abstract":"<div><h3>Background</h3><div>The characterization of physiological immune signatures in a population-based cohort is a prerequisite for identifying pathological immune signatures associated with inflammatory or autoimmune diseases.</div></div><div><h3>Methods</h3><div>Here, 47 plasma cytokines, chemokines, and growth factors were quantified with a bead-based multiplex-assay (Merck HCYTA-60 K) using a FLEXMAP 3D™ instrument in 1175 individuals of the Study of Health in Pomerania (SHIP; TREND cohort, 532 men and 643 women, age: 20 to 81, BMI: 17.7 to 53.6). Associations of cytokine concentrations with age, sex, BMI, season, and blood cell parameters (BCP) were examined by multivariate regression models.</div></div><div><h3>Results</h3><div>The physiological cytokine concentrations differed strongly between analytes, with median concentrations ranging from 0.6 to 7820 pg/mL. Many cytokine levels showed a large dynamic range within the study population. Higher levels of the pro-inflammatory cytokines and chemokines IL-6, IL-8, CXCL9, CXCL10, IL-12p40, CCL2, CCL4, CCL11, IL-27, FLT3LG, and TNFα were significantly associated with increasing age. The strongest age-associated effects were seen for CXCL9 (β_st = 0.4, <em>p</em> &lt; 0.001) and CXLC10 (β_st = 0.3, p &lt; 0.001). Significant sex differences were detected for CCL2, CCL3, CCL4, CCL11, CCL22, IL-12p40, IL-1RA, IL-18, IL-27, and TNFα levels among which CCL11 showed the strongest effect (β_st = −0.24, <em>p</em> &lt; 0.001) with a lower level in women compared to men. Moreover, seven cytokines and chemokines, i.e. CCL4, CCL22, CXCL10, IL-1RA, IL-18, IL-6, and TNFα, displayed higher levels with increasing BMI. Among those, the strongest effect was seen for IL-1RA (β_st = 0.19, <em>p</em> &lt; 0.001), CCL4 (β_st = 0.16, p &lt; 0.001) and CXCL10 (β_st = 0.14, p &lt; 0.001). Only CCL11 (β_st = −0.17, p &lt; 0.001) decreased with increasing BMI. Subjects categorized as obese exhibited significantly elevated levels of CCL4, CCL22, CXCL10, and IL-1RA, while only CCL11 showed significantly reduced levels compared to normal weight. Certain cytokines such as IL-6, IL-18, or TNFα showed decreased significance levels after adjustment for blood cell components indicating blood cell components (BCPs) as potential confounders. We observed no significant non-linear seasonal effects for the investigated cytokines.</div></div><div><h3>Conclusion</h3><div>The generated cytokine atlas provides detailed information on cytokine variations in the general population and will provide a reference base for disease-related studies in the future. Furthermore, BCPs should be considered as potential confounders in association studies based on plasma cytokine levels.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"189 ","pages":"Article 156896"},"PeriodicalIF":3.7,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143509851","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":"The role of cytokines in shaping the future of Cancer immunotherapy","authors":"Sahar Safaei ,&nbsp;AmirHossein Yari ,&nbsp;Omid Pourbagherian ,&nbsp;Leili Aghebati Maleki","doi":"10.1016/j.cyto.2025.156888","DOIUrl":"10.1016/j.cyto.2025.156888","url":null,"abstract":"<div><div>As essential immune system regulators, cytokines are essential for modulating both innate and adaptive immunological responses. They have become important tools in cancer immunotherapy, improving the immune system's capacity to identify and destroy tumor cells. This article examines the background, workings, and therapeutic uses of cytokines, such as interleukins, interferons, and granulocyte-macropHage colony-stimulating factors, in the management of cancer. It examines the many ways that cytokines affect immune cell activation, signaling pathways, tumor development, metastasis, and prognosis by modifying the tumor microenvironment. Despite the limited effectiveness of cytokine-based monotherapy, recent developments have concentrated on new fusion molecules such as immunocytokines, cytokine delivery improvements, and combination techniques to maximize treatment efficacy while reducing adverse effects. Current FDA-approved cytokine therapeutics and clinical trial results are also included in this study, which offers insights into how cytokines might be used with other therapies including checkpoint inhibitors, chemotherapy, and radiation therapy to address cancer treatment obstacles. This study addresses the intricacies of cytokine interactions in the tumor microenvironment, highlighting the possibility for innovative treatment methods and suggesting fresh techniques for enhancing cytokine-based immunotherapies. PEGylation, viral vector-mediated cytokine gene transfer, antibody-cytokine fusion proteins (immunocytokines), and other innovative cytokine delivery techniques are among the novelties of this work, which focuses on the most recent developments in cytokine-based immunotherapy. Additionally, the study offers a thorough examination of the little-reviewed topic of cytokine usage in conjunction with other treatment techniques. It also discusses the most recent clinical studies and FDA-approved therapies, providing a modern perspective on the developing field of cancer immunotherapy and suggesting creative ways to improve treatment effectiveness while lowering toxicity.</div></div><div><h3>Background</h3><div>Cytokines are crucial in cancer immunotherapy for regulating immune responses and modifying the tumor microenvironment (TME). However, challenges with efficacy and safety have driven research into advanced delivery methods and combination therapies to enhance their therapeutic potential.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"189 ","pages":"Article 156888"},"PeriodicalIF":3.7,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143488271","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":"Inhibition of inflammation by IL-6 blockade in xenotransplantation","authors":"Zuzanna Iwanczyk ,&nbsp;Hidetaka Hara ,&nbsp;David K.C. Cooper ,&nbsp;Akihiro Maenaka","doi":"10.1016/j.cyto.2025.156897","DOIUrl":"10.1016/j.cyto.2025.156897","url":null,"abstract":"<div><div>The inflammatory cytokine interleukin 6 (IL-6) plays a role in both acute and chronic organ allotransplant rejection. Data suggest that IL-6 inhibition may help prevent or reverse rejection, with large multi-center trials now underway. However, the evidence for the benefit of IL-6 inhibitors in xenotransplantation is limited. IL-6 inhibition has been explored in nonhuman-primate models of xenotransplantation, but no clear consensus exists on its efficacy or the best mode of IL-6 inhibition (anti-IL-6 antibodies, or through IL-6 receptor [IL-6R] blockade).</div><div>Extra considerations for IL-6 blockade exist in xenotransplantation, as both recipient (human) and xenograft-derived (porcine) IL-6 may play roles. The systemic inflammation seen in xenograft recipients (SIXR) contributes to significant morbidity and mortality for the recipient through coagulation dysfunction and augmentation of the immune response. Anti-IL-6 antibodies (e.g., siltuximab) bind to human IL-6 and prevent IL-6R activation, but do not bind to porcine IL-6, and so have no effect in preventing graft-driven inflammatory processes. In contrast, IL-6R inhibitors (e.g., tocilizumab) inhibit IL-6 activity by blocking binding of human and porcine IL-6 to human IL-6R. Although IL-6R blockade cannot prevent the effect of IL-6 on porcine cells, it probably prevents graft-derived IL-6 from contributing to an inflammatory response in the host.</div><div>This review outlines the role of IL-6 in xenotransplantation and discusses mechanisms for inhibiting IL-6 to improve recipient survival.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"189 ","pages":"Article 156897"},"PeriodicalIF":3.7,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143480337","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":"Evaluating the evidence for GM-CSF as a host-directed therapy in respiratory infections","authors":"Camille David ,&nbsp;Charles Verney ,&nbsp;Mustapha Si-Tahar ,&nbsp;Antoine Guillon","doi":"10.1016/j.cyto.2025.156902","DOIUrl":"10.1016/j.cyto.2025.156902","url":null,"abstract":"<div><div>Novel therapeutic approaches are needed to treat respiratory infections due to the rising antimicrobial resistance and the lack of effective antiviral therapies. A promising avenue to overcome treatment failure is to develop strategies that target the host immune response rather than the pathogen itself. Granulocyte-macrophage colony-stimulating factor (GM-CSF) plays a critical role in controlling homeostasis in lungs, alveolar macrophages being the most sensitive cells to GM-CSF signaling. In this review, we discuss the importance of GM-CSF secretion for lung homeostasis and its alteration during respiratory infections. We also present the pre-clinical evidence and clinical investigations evaluating GM-CSF-based treatments (administration or inhibition) as a therapeutic strategy for treating respiratory infections, highlighting both supporting and contradictory findings.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"189 ","pages":"Article 156902"},"PeriodicalIF":3.7,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143480336","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":"Microglial pyroptosis induced by SENP7 via the cGAS/STING/IRF3 pathway contributes to neuronal apoptosis","authors":"Lin Liu ,&nbsp;Fei Xiao ,&nbsp;Jinyue Yang ,&nbsp;Hanqing Yao ,&nbsp;Ke Hua","doi":"10.1016/j.cyto.2025.156893","DOIUrl":"10.1016/j.cyto.2025.156893","url":null,"abstract":"<div><h3>Background</h3><div>Maternal anesthetic exposure may exacerbate significant neurocognitive risks in the immature brains of fetuses. However, the mechanisms through which sevoflurane exposure during pregnancy results in cognitive impairments in offspring remain unclear.</div></div><div><h3>Methods</h3><div>Pregnant C57BL/6 mice (gestational day 14) were intervented with 2.5 % sevoflurane for 6 h. Morris water maze test and context fear conditioning test were utilized to evaluate the cognitive function of the offspring. BV2 cells were stimulated with LPS-ATP to evaluate the impacts of SENP7 on microglial pyroptosis. A co-culture experiment was conducted to investigate the apoptosis of mouse hippocampal neuronal cells induced by BV2 cells. The regulatory roles of SENP7 in the cGAS/STING/IRF3 pathway were assessed using an immunoprecipitation SUMOylation assay, along with Western blot analysis.</div></div><div><h3>Results</h3><div>Sevoflurane exposure during pregnancy resulted in cognitive impairments in offspring mice, which were associated with the upregulation of SENP7, Iba1, Caspase1, and GSDMD-N proteins, as well as the downregulation of NeuN and TH proteins in the brains of the offspring. The knockdown of SENP7 inhibited the elevation of GSDMD-N, Caspase1, and NLRP3 protein levels, subsequently reducing the concentrations of IL-1β and IL-18 in BV2 cells induced by LPS-ATP. Furthermore, SENP7 facilitated the activation of the cGAS/STING/IRF3 axis by regulating the deSUMOylation of cGAS, which triggered microglial pyroptosis and subsequently led to neuronal apoptosis.</div></div><div><h3>Conclusion</h3><div>Maternal exposure to sevoflurane increased the expression of SENP7 in the brains of offspring and resulted in detrimental effects on cognitive function. This phenomenon was associated with neuronal apoptosis triggered by microglial pyroptosis, which was regulated by SENP7 through the cGAS/STING/IRF3 pathway.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"189 ","pages":"Article 156893"},"PeriodicalIF":3.7,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143480386","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":"Seasonal variation in the associations between self-reported long-COVID symptoms and IL-6 signalling-related factors (particularly the rs2228145 variant of the IL-6R gene): A clinical study.","authors":"Katie Rees ,&nbsp;Rebecca Aicheler ,&nbsp;Lee Butcher ,&nbsp;Alan Dodd ,&nbsp;John Geen ,&nbsp;Ceri Lynch ,&nbsp;Isabel Massey ,&nbsp;Keith Morris ,&nbsp;Brian Tennant ,&nbsp;Richard Webb","doi":"10.1016/j.cyto.2025.156884","DOIUrl":"10.1016/j.cyto.2025.156884","url":null,"abstract":"<div><div>This observational study focused on the impact of Interleukin-6 (IL-6)-related factors (notably the IL-6 receptor (IL-6R) gene's rs2228145 polymorphism) on long-COVID risk in individuals who had previously experienced COVID-19 infection(s). The purpose of the study was to better understand such factors' contribution to long-COVID risk, and thus possibly initiate future strategies for using IL-6-related factors as biomarkers predictive of risk (while also obtaining data that may influence long-COVID management and treatment more generally).</div><div>DNA and blood samples, plus questionnaire responses regarding long-COVID symptoms (including chronic fatigue and cognitive impairment), were collected from 175 participants who had previously experienced COVID-19 infection(s). Potential associations between self-reported long-COVID symptoms and participants' rs2228145 genotypes (determined using TaqMan-based genotyping assays) and/or their circulating IL-6, sIL-6R and sgp130 levels (determined using ELISA) were evaluated.</div><div>Univariate-regression analyses demonstrated that odds of exhibiting long-COVID symptoms increased with severity/number of previous COVID-19 infection(s) and with hypertension as a co-morbidity, while vaccination decreased the likelihood of developing long-COVID. While long-COVID sufferers exhibited higher IL-6 signalling activity than healthy control individuals, rs2228145 genotype was not associated with long-COVID odds-ratios in- the entire-study cohort. Following identification of significant seasonal variations within our dataset, the entire-study cohort was stratified depending on when samples/questionnaire responses were obtained. In the resulting ‘summer’ sub-cohort (but not the ‘winter’ sub-cohort), the rs2228145 AA genotype was significantly over-represented amongst those exhibiting long-COVID symptoms, and long-COVID odds-ratios were significantly reduced for the CC and AC genotypes.</div><div>While interpretation is complicated by seasonal variations, these findings may be of medical/biomedical value. Importantly, as IL-6 was higher in long-COVID sufferers than healthy controls, and rs2228145 AA genotype-bearing individuals within our ‘summer’ sub-cohort were at elevated risk of developing long-COVID, these findings point towards possible future use of IL-6 and/or rs2228145 genotype as biomarkers predictive of long-COVID risk, which may bring advantages regarding management and treatment of long-COVID.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"189 ","pages":"Article 156884"},"PeriodicalIF":3.7,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143471280","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":"Circulating inflammatory cytokines and risk of aortic stenosis: A Mendelian randomization analysis","authors":"Xiaohan Qiu ,&nbsp;Jijun Wu ,&nbsp;Zehao Chen ,&nbsp;Yu Zhang ,&nbsp;Luying Cao ,&nbsp;Ning Wang ,&nbsp;Junlin Teng ,&nbsp;Cong Su ,&nbsp;Congyi Cheng ,&nbsp;Fen Wang ,&nbsp;Wenqiang Chen","doi":"10.1016/j.cyto.2025.156887","DOIUrl":"10.1016/j.cyto.2025.156887","url":null,"abstract":"<div><h3>Background</h3><div>Observational studies have consistently reported positive associations between inflammatory biomarkers and the risk of developing aortic stenosis (AS). However, it is crucial to acknowledge that conventional observational studies are prone to various forms of bias, including reverse causation and residual confounding. To delve deeper into unraveling the potential causal relationship between inflammatory biomarkers and aortic stenosis, we conducted a comprehensive two-sample Mendelian randomization (MR) analysis.</div></div><div><h3>Methods</h3><div>In order to explore the causal effect of exposure to various circulating cytokines on the risk of developing AS, we carefully selected AS datasets as the exposures from the summary statistics of the genome-wide association study (GWAS) conducted by FinnGen. The dataset consisted of a sample size of 3283 for AS cases and 210,463 for controls. To estimate the MR analysis, we primarily adopted the inverse variance weighted (IVW) method. Additionally, we employed complementary methods, including Weighted Median, MR Egger, Weighted Mode, and Simple Mode, to analyze the causal associations comprehensively. In order to assess the presence of heterogeneity, we utilized Cochran's Q statistic and MR-Egger regression. To ensure the robustness and consistency of our findings, we conducted a leave-one-out analysis.</div></div><div><h3>Result</h3><div>We observed a positive association between interleukin-18 (IL-18) levels and AS (odds ratio [OR] per standard deviation [SD] = 1.080; 95 % confidence interval [CI] 1.024 to 1.139), as well as between interferon-gamma levels (IFN-γ) and AS (OR per SD = 1.157; 95 % CI 1.028 to 1.302). Conversely, we found an inverse association between interleukin-13 (IL-13) levels and AS (OR per SD = 0.942; 95 % CI 0.890 to 0.997), as well as between interleukin-5 (IL-5) levels and AS (OR per SD = 0.892; 95 % CI 0.804 to 0.990).</div></div><div><h3>Conclusion</h3><div>Our research enhances the current understanding of the role of specific inflammatory biomarker pathways in aortic stenosis. Nevertheless, further validation is required to assess the viability of targeting these cytokines through pharmacological or lifestyle interventions as potential treatments for aortic stenosis.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"189 ","pages":"Article 156887"},"PeriodicalIF":3.7,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143463816","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":"LINC-PINT suppresses the progression of acute myeloid leukemia via miR-767-5p/SUZ12-mediated JAK/STAT signaling pathway","authors":"Lei Xiang ,&nbsp;Xue Lin ,&nbsp;Yong Wu","doi":"10.1016/j.cyto.2025.156883","DOIUrl":"10.1016/j.cyto.2025.156883","url":null,"abstract":"<div><h3>Background</h3><div>Long noncoding RNA (lncRNA) long intergenic non-protein-coding RNA, p53-induced transcript (LINC-PINT) has shown a crucial role in cancer cells. However, its function in acute myeloid leukemia (AML) is unclear.</div></div><div><h3>Methods</h3><div>The expression levels of LINC-PINT and miR-767-5p in AML patients were measured through quantitative real-time PCR. The interaction between miR-767-5p and LINC-PINT or suppressor of zeste 12 (SUZ12) was verified by RNA immunoprecipitation (RIP) assay and luciferase reporter assay. SUZ12-mediated JAK/STAT signaling pathway was further confirmed using western blotting and immunoprecipitation. Cell proliferation, cell cycle distribution, and apoptosis were evaluated by CCK-8 and flow cytometry. Tumor formation was examined by a nude mice model in vivo.</div></div><div><h3>Results</h3><div>The low expression of LINC-PINT was significantly related to ELN risk stratification (<em>p</em> = 0.028). Ectopic expression of LINC-PINT restrained the proliferation and cell cycle G1/S transition and promoted apoptosis in AML cell lines (THP-1 and HL-60). LINC-PINT overexpression curbed tumor growth. LINC-PINT positively regulated SUZ12 by functioning as a sponge of miR-767-5p. There was a negative correlation between miR-767-5p and LINC-PINT in AML (<em>r</em> = −0.3316, <em>p</em> = 0.0336). Co-expression of miR-767-5p reversed the impacts of LINC-PINT on AML cells. MiR-767-5p enhanced the aggressiveness of AML, which was counteracted by overexpression of SUZ12. Additionally, SUZ12 downregulated HDAC1 to reduce STAT3 phosphorylation and acetylation in AML cells.</div></div><div><h3>Conclusions</h3><div>Overall, LINC-PINT serves as a tumor suppressor in AML through the miR-767-5p/SUZ12-mediated JAK/STAT signaling pathway, presenting a potential therapeutic target for AML.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"188 ","pages":"Article 156883"},"PeriodicalIF":3.7,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143445419","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":"Investigation of TNF and related lncRNAs in diabetic nephropathy","authors":"Seyed Mohsen Aghaei-Zarch ,&nbsp;Leila Mahmoudieh ,&nbsp;Mohammad Miryounesi ,&nbsp;Maryam Aghazadeh ,&nbsp;Mehran Reihani-Ardabili ,&nbsp;Marzieh Zamani ,&nbsp;Marzieh Motallebi ,&nbsp;Abolfazl Movafagh","doi":"10.1016/j.cyto.2025.156892","DOIUrl":"10.1016/j.cyto.2025.156892","url":null,"abstract":"<div><h3>Background</h3><div>Diabetic nephropathy (DN) is a significant driver of end-stage renal disease, requiring kidney replacement therapies such as transplantation and dialysis. Given the critical importance of understanding the onset and progression of DN, we sought to explore the expression levels of tumor necrosis factor (TNF) and related long noncoding RNAs (lncRNAs) in diabetic patients with and without DN, as well as in pre-diabetic individuals, compared to healthy controls. We further explored the involvement of TNF and TNF-related lncRNAs in high glucose (HG)-induced apoptosis of human embryonic kidney (HEK)-293 cells.</div></div><div><h3>Material and method</h3><div>In the current cross-sectional investigation, we compare the expression levels of lncRNA myocardial infarction-associated transcript (MIAT), lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1), and TNF in 50 healthy individuals, 50 people with prediabetes, 50 patients with type 2 diabetes mellitus (T2DM), and 50 patients with T2DM- DN. We cultured HEK293 cells in a HG condition (100 mM glucose) to establish a cellular model of DN, while HEK293 cells cultured in a normal-glucose environment (5 mM glucose) served as controls. We further assess apoptosis in HEK293 cells via flow cytometry analysis. Moreover, we evaluated the expression levels of lncRNA MIAT, lncRNA NEAT1, and TNF in HG and normal-glucose (NG) groups to investigate their potential involvement in HEK293 cell apoptosis and the pathogenesis of DN.</div></div><div><h3>Result</h3><div>Our findings reveal a significant upregulation of lncRNA MIAT, lncRNA NEAT1, and TNF in T2DM and T2DM-associated DN groups compared to prediabetic individuals and healthy controls (<em>p</em> &lt; 0.05). Furthermore, HG conditions significantly increased the apoptotic rate of HEK293 cells. Additionally, the expression levels of TNF, lncRNA MIAT, and lncRNA NEAT1 were increased in HEK-293 cells cultured in a HG.</div></div><div><h3>Conclusion</h3><div>In conclusion, our findings indicate a significant role for the TNF gene and associated lncRNAs, such as lncRNA MIAT and lncRNA NEAT1, in podocyte apoptosis and the development of DN.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"188 ","pages":"Article 156892"},"PeriodicalIF":3.7,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143429617","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":"The intricate ballet of inflammation and autophagy: Insights from Mycoplasma gallisepticum-infected HD11 cells","authors":"Yuquan Guo ,&nbsp;Wanying Hu ,&nbsp;Jiaqi Hu,&nbsp;Shun Wang,&nbsp;Rui Li,&nbsp;Jichang Li,&nbsp;Jiaxin Bao,&nbsp;Chunli Chen","doi":"10.1016/j.cyto.2025.156895","DOIUrl":"10.1016/j.cyto.2025.156895","url":null,"abstract":"<div><h3>Objectives</h3><div><em>Mycoplasma gallisepticum</em> (<em>M. gallisepticum</em>) infection often leads to inflammatory damage and immunosuppression. Macrophages play a crucial role as the primary immune defense in chickens, with their inflammatory response and autophagy levels critical. This study aimed to explore the relationship between NLRP3 inflammasome and autophagy in HD11 cells within 12 h after <em>M. gallisepticum</em> infection.</div></div><div><h3>Methods</h3><div>To investigate this, the HD11 cell model of <em>M. gallisepticum</em> infection was established using the CCK8 (Cell Counting Kit-8) method in this study. The study observed changes in <em>M. gallisepticum</em>-induced inflammation, oxidative stress, and autophagy levels through various methods including transmission electron microscopy (TEM), RT-qPCR, ELISA (enzyme linked immunosorbent assay), 2′,7′-dichlorodihydrofluorescein diacetate (DCFH-DA), JC-1 and Western blot.</div></div><div><h3>Results</h3><div>TEM revealed that the nuclear membrane was damaged, the number of damaged mitochondria increased, and autophagosomes were detected at 4 and 8 h after <em>M. gallisepticum</em> infection. ELISA and RT-qPCR results indicated that <em>M. gallisepticum</em> induced oxidative stress and inflammation damage. Fluorescence analysis demonstrated an increase in intracellular reactive oxygen species (ROS) content and a continuous decrease in mitochondrial membrane potential (MMP) post-<em>M. gallisepticum</em> infection. Additionally, the NF-κB/NLRP3 signaling pathway remained consistently activated during <em>M. gallisepticum</em> infection. After <em>M. gallisepticum</em> infection, autophagy levels decreased significantly at 1 and 12 h, but increased significantly at 4 and 8 h.</div></div><div><h3>Conclusions</h3><div><em>M. gallisepticum</em> infection triggers the activation of the NLRP3 inflammasome in HD11 cells, leading to inflammatory damage. Additionally, it causes fluctuations in autophagy levels, characterized by a wavy pattern of decrease, increase, and subsequent decrease.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"188 ","pages":"Article 156895"},"PeriodicalIF":3.7,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143436898","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}