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Exosomes from renal cells and macrophages: Bidirectional communication in the pathogenesis of kidney disease 肾细胞和巨噬细胞外泌体:肾脏疾病发病机制中的双向交流
IF 3.7 3区 医学
Cytokine Pub Date : 2025-05-17 DOI: 10.1016/j.cyto.2025.156961
Jing Gao , Pan Chen , Wen-jing Zhao , Hong-wei Su , Li Wang , Rui-zhi Tan , Jian Liu
{"title":"Exosomes from renal cells and macrophages: Bidirectional communication in the pathogenesis of kidney disease","authors":"Jing Gao ,&nbsp;Pan Chen ,&nbsp;Wen-jing Zhao ,&nbsp;Hong-wei Su ,&nbsp;Li Wang ,&nbsp;Rui-zhi Tan ,&nbsp;Jian Liu","doi":"10.1016/j.cyto.2025.156961","DOIUrl":"10.1016/j.cyto.2025.156961","url":null,"abstract":"<div><div>Macrophages are key cells in the immune response, and their abnormal infiltration into the kidney is a common pathological feature in kidney diseases. Exosomes, acting as carriers for transporting essential proteins and genetic materials, can be derived from various cell types and are involved in a wide range of physiological and pathological processes in the kidney. As primary inflammatory immune cells, macrophages have garnered significant attention from scholars regarding the effects of their secreted exosomes on renal intrinsic cells in kidney diseases, as well as the interactive effects of exosomes derived from other cells on macrophages. This review delves into the detailed characteristics of macrophage-derived exosomes in kidney diseases, the mechanisms by which they promote damage to specific cells, and the signaling pathways involved. Additionally, it examines the reverse direction, elucidating the circulatory mechanisms of substances carried by exosomes from renal intrinsic cells that induce phenotypic transformation and inflammatory responses in macrophages, ultimately leading to further damage of renal intrinsic cells. The pathological role of exosome-macrophage interconnections in various renal diseases has received increasing attention, and understanding this mechanism can help unravel the microscopic immunoregulatory processes underlying kidney diseases. Moreover, the identification of therapeutic targets related to macrophage-related exosomes offers new strategies for the treatment of these conditions.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"192 ","pages":"Article 156961"},"PeriodicalIF":3.7,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144072087","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}
引用次数: 0
Study on the correlation between intestinal flora and cytokines in children with Henoch-Schönlein purpura Henoch-Schönlein紫癜患儿肠道菌群与细胞因子的相关性研究
IF 3.7 3区 医学
Cytokine Pub Date : 2025-05-14 DOI: 10.1016/j.cyto.2025.156959
Mingxin Liang , Zhaoxu Deng , Weiyi Wu , Qinqin Dong , Juan Fan
{"title":"Study on the correlation between intestinal flora and cytokines in children with Henoch-Schönlein purpura","authors":"Mingxin Liang ,&nbsp;Zhaoxu Deng ,&nbsp;Weiyi Wu ,&nbsp;Qinqin Dong ,&nbsp;Juan Fan","doi":"10.1016/j.cyto.2025.156959","DOIUrl":"10.1016/j.cyto.2025.156959","url":null,"abstract":"<div><h3>Background</h3><div>The pathogenesis of Henoch-Schönlein purpura (HSP) is complex. It is currently believed that the development of HSP involves abnormalities in humoral immunity and cellular immunity. The intestinal microbiota has a powerful regulatory effect on the human immune system and has been shown to serve a significant role in the pathogenesis of various immune-mediated disorders. This study examines changes in intestinal flora and cytokines(IFN-γ, IL-4, IL-10, and IL-17) in children with HSP and explores their correlation, offering fresh insights for the prevention and treatment of HSP. METHODS: Blood and stool specimens were collected from 25 healthy children (control group) and 27 children with HSP (observation group). Enzyme-linked immunosorbent assay(ELISA) was used to detect the levels of cytokines IFN-γ, IL-4, IL-17, and IL-10 in the serum of all the study participants, and the 16S rRNA gene sequencing combined with high-throughput sequencing technology was used to analyze the intestinal flora of the study subjects. Finally, the correlation between serum cytokines and gut microbiota was analyzed in the children with HSP. RESULT:1)The serum levels of IL-4 and IL-17 in the observation group were higher than those in the control group, while the levels of IFN-γ and IL-10 were lower than those in the control group. 2) At the level of phylum, the abundance of <em>Fusobacteria</em> and <em>Verrucomicrobia</em> was higher than that in the control group, while the abundance of <em>Firmicutes</em> was lower than that of the control group, and the differences were statistically significant (<em>P</em> &lt; 0.05); At the level of genus, the abundance of <em>Prevotella</em> and <em>Akkermansia</em> were higher than the control group, while the abundance of <em>Bifidobacterium</em>, <em>Blautia</em>, and <em>Clostridium</em> XlVa was lower than that in the control group, and the differences were all statistically significant (<em>P</em> &lt; 0.05); At the species level, the abundance of <em>Akkermansia muciniphila</em>, <em>Prevotella copri</em>, and <em>Subdoligranulum variabile</em> was higher than that of the control group, while the abundance of <em>Bifidobacterium pseudolongum</em>, <em>Brautella Weiss</em>, and <em>Bacteroides fragilis</em> was lower than that in the control group, and the differences were statistically significant (<em>P</em> &lt; 0.05). 3) The abundance of <em>Blautia</em> and <em>Blautia wexlerae</em> in the observation group was positively associated with the IL-10 level (<em>r</em> = 0.522, <em>r</em> = 0.578, <em>P</em> &lt; 0.01). CONCLUSION: Disturbances in intestinal flora and changes in serum cytokines IFN-γ, IL-4, IL-10, and IL-17 were present in children with HSP. The abundance of <em>Blautia</em> and <em>Blautia wexlerae</em> in the gut microbiota of children with HSP was positively correlated with serum IL-10 levels.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"191 ","pages":"Article 156959"},"PeriodicalIF":3.7,"publicationDate":"2025-05-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143941119","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}
引用次数: 0
Molecular insights into diabetic wound healing: Focus on Wnt/β-catenin and MAPK/ERK signaling pathways 糖尿病伤口愈合的分子机制:关注Wnt/β-catenin和MAPK/ERK信号通路
IF 3.7 3区 医学
Cytokine Pub Date : 2025-05-13 DOI: 10.1016/j.cyto.2025.156957
Shricharan Pandey , Tushar Anshu , Krushna Ch. Maharana , Suhani Sinha
{"title":"Molecular insights into diabetic wound healing: Focus on Wnt/β-catenin and MAPK/ERK signaling pathways","authors":"Shricharan Pandey ,&nbsp;Tushar Anshu ,&nbsp;Krushna Ch. Maharana ,&nbsp;Suhani Sinha","doi":"10.1016/j.cyto.2025.156957","DOIUrl":"10.1016/j.cyto.2025.156957","url":null,"abstract":"<div><div>Diabetic wounds manifest significant clinical challenge with approximately 50–70 % reporting non-traumatic lower limb amputations annually. This review examines the intricate relationship between impaired wound healing in diabetes mellitus and two crucial signaling pathways: Wnt/β-catenin and MAPK/ERK. Chronic hyperglycemia in diabetes mellitus leads to peripheral neuropathy, vascular dysfunction, and compromised immune responses, resulting in delayed wound healing. The Wnt/β-catenin pathway, which is essential for cellular proliferation, differentiation, and tissue homeostasis, shows altered activity in diabetic wounds, particularly through decreased R-spondin 3 protein expression. Similarly, the MAPK/ERK pathway, which regulates cellular proliferation and differentiation through hierarchical kinase cascades, exhibits dysregulation under diabetic conditions. This review describes the current understanding of normal wound healing processes, diabetic wound pathophysiology, and the molecular mechanisms of both signaling pathways. Evidence suggests that targeting these pathways, either individually or synergistically offer promising therapeutic approaches for diabetic wound management. Future directions include, developing targeted delivery systems, exploring pathway cross-talk, and investigating dual-pathway modulators to enhance wound healing outcomes in diabetic patients. This comprehensive analysis provides insights into potential therapeutic strategies and emphasizes the necessity of research in this crucial area of diabetes treatment. (Graphical Abstract)</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"191 ","pages":"Article 156957"},"PeriodicalIF":3.7,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143941116","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}
引用次数: 0
FokI polymorphism of the vitamin D receptor gene: Linking COVID-19 risk to genetic susceptibility in children 维生素D受体基因的FokI多态性:将COVID-19风险与儿童遗传易感性联系起来
IF 3.7 3区 医学
Cytokine Pub Date : 2025-05-13 DOI: 10.1016/j.cyto.2025.156958
Amal Ahmed Mohamed , Abdullah Taher Alanazi , Hoda H. Ahmed , Samar Elfiky , Muhammad T Abdel Ghafar , Ingy Maher , Sherin A. Taha , Mohammed Zakaria Ali AbuRahma , Waleed Elagawy , Dina A. Mohareb , Abeer M. Rawy , Heba M. Abostate , Amira AlSayed Youssef , Dalia Saeed Elsayed , Rasha M. Abdel-Hamid
{"title":"FokI polymorphism of the vitamin D receptor gene: Linking COVID-19 risk to genetic susceptibility in children","authors":"Amal Ahmed Mohamed ,&nbsp;Abdullah Taher Alanazi ,&nbsp;Hoda H. Ahmed ,&nbsp;Samar Elfiky ,&nbsp;Muhammad T Abdel Ghafar ,&nbsp;Ingy Maher ,&nbsp;Sherin A. Taha ,&nbsp;Mohammed Zakaria Ali AbuRahma ,&nbsp;Waleed Elagawy ,&nbsp;Dina A. Mohareb ,&nbsp;Abeer M. Rawy ,&nbsp;Heba M. Abostate ,&nbsp;Amira AlSayed Youssef ,&nbsp;Dalia Saeed Elsayed ,&nbsp;Rasha M. Abdel-Hamid","doi":"10.1016/j.cyto.2025.156958","DOIUrl":"10.1016/j.cyto.2025.156958","url":null,"abstract":"<div><h3>Background</h3><div>Vitamin D receptor (VDR), influenced by gene polymorphisms like <em>FokI</em>, may affect susceptibility to infections, including coronavirus disease 2019 (COVID-19). Since studies in children are limited, we aimed to analyze the correlation between the VDR <em>FokI</em> variant and both the incidence and severity of COVID-19 in Egyptian children.</div></div><div><h3>Methods</h3><div>Seventy-seven COVID-19-positive and 107 COVID-19-negative pediatric patients were included. Participants' serum 25(OH)D levels, inflammatory biomarkers, and demographics were evaluated. Real-time polymerase chain reaction (PCR) was used for genotyping the VDR <em>FokI</em> (rs2228570) polymorphism.</div></div><div><h3>Results</h3><div>Absolute lymphocyte count (ALC) was significantly lower in COVID-19 patients than in controls, while interleukin-6 (IL-6), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), procalcitonin, and D-dimer were significantly higher (all <em>p</em> &lt; 0.001). Vitamin D insufficiency was significantly more common in COVID-19 cases (18.2 % versus 3.7 %, <em>p</em> = 0.002). Male sex, increased tumor necrosis factor-alpha (TNF-α), and CRP were significantly associated with severe COVID-19 (<em>p</em> = 0.032, 0.029, &lt; 0.001, respectively). The <em>FokI</em> TT genotype in codominant and recessive models and the T allele in the multiplicative model were significantly correlated with 2.4, 3.0, and 1.8 folds increased COVID-19 risk (<em>p</em> = 0.043, &lt; 0.001, and 0.004, respectively). However, VDR <em>FokI</em> variants did not significantly associate with severe COVID-19.</div></div><div><h3>Conclusion</h3><div>The T allele and TT genotype of the <em>FokI</em> variant in the <em>VDR</em> gene increase susceptibility to COVID-19 but not its severity in Egyptian children. Additional research is required to validate the potential role of vitamin D and its receptor polymorphism in COVID-19.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"191 ","pages":"Article 156958"},"PeriodicalIF":3.7,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143941118","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}
引用次数: 0
Eliminating myeloid-derived suppressor cells alleviates immunosuppression and reduces susceptibility to secondary infections in a two-hit sepsis model 消除髓源性抑制细胞减轻免疫抑制和降低易感性继发感染在一个两击败血症模型
IF 3.7 3区 医学
Cytokine Pub Date : 2025-05-08 DOI: 10.1016/j.cyto.2025.156955
Dongjie Liu , Wei Fu , Teng Zhang , Jianyao Wang , Yuxin He , Xiao Wang , Tongxiang Xu , Cheng Wang , Tao Ma
{"title":"Eliminating myeloid-derived suppressor cells alleviates immunosuppression and reduces susceptibility to secondary infections in a two-hit sepsis model","authors":"Dongjie Liu ,&nbsp;Wei Fu ,&nbsp;Teng Zhang ,&nbsp;Jianyao Wang ,&nbsp;Yuxin He ,&nbsp;Xiao Wang ,&nbsp;Tongxiang Xu ,&nbsp;Cheng Wang ,&nbsp;Tao Ma","doi":"10.1016/j.cyto.2025.156955","DOIUrl":"10.1016/j.cyto.2025.156955","url":null,"abstract":"<div><div>Myeloid-derived suppressor cells (MDSCs) are known for their immunosuppressive effects on both innate and adaptive immunity, particularly targeting T cells, and they undergo continuous expansion during sepsis. However, the pathophysiological significance of MDSCs in sepsis-induced immunosuppression remains to be fully elucidated. In this study, we investigated the dynamic changes in MDSCs during sepsis and their contribution to sepsis-induced immunosuppression using a clinically relevant “two-hit” sepsis model. Our findings revealed that mice surviving cecal ligation and puncture (CLP) exhibited a significant accumulation and enhanced activity of MDSCs, which correlated with sepsis-related immune paralysis, impaired bacterial clearance, and heightened susceptibility to secondary infections. Importantly, administration of the liver X receptor (LXR) agonist GW3965 at the late stage of sepsis significantly restored immune function, decreased susceptibility to secondary infections, enhanced bacterial clearance, and improved prognosis by eliminating MDSCs. These results highlight the pivotal role of MDSCs in the development of sepsis-associated immunosuppression and indicate that targeting MDSCs could be a promising therapeutic approach to mitigate immunosuppression in sepsis.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"191 ","pages":"Article 156955"},"PeriodicalIF":3.7,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143917576","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}
引用次数: 0
Mesenchymal stem cell transplantation ameliorates inflammation in spinal cord injury by inhibiting lactylation-related genes 间充质干细胞移植通过抑制乳酸化相关基因改善脊髓损伤的炎症
IF 3.7 3区 医学
Cytokine Pub Date : 2025-05-08 DOI: 10.1016/j.cyto.2025.156960
Weiwei Zou , Zelin Zhang , Tingting Cao , Mangmang Li
{"title":"Mesenchymal stem cell transplantation ameliorates inflammation in spinal cord injury by inhibiting lactylation-related genes","authors":"Weiwei Zou ,&nbsp;Zelin Zhang ,&nbsp;Tingting Cao ,&nbsp;Mangmang Li","doi":"10.1016/j.cyto.2025.156960","DOIUrl":"10.1016/j.cyto.2025.156960","url":null,"abstract":"<div><h3>Background</h3><div>The immune microenvironment significantly influences neural regeneration in spinal cord injury (SCI). Lactate activates central nervous system (CNS) glial cells, prompting the secretion of proinflammatory cytokines and triggering an inflammatory response. Mesenchymal stem cells (MSCs) make a promising future for SCI therapy due to their immune regulation and anti-inflammatory properties. However, it is unclear whether MSCs inhibit inflammatory responses in the SCI microenvironment through lactylation regulation. This study aimed to identify lactylation-related genes (LRGs) in SCI and investigate their role in immune cell infiltration and MSC-mediated inflammation reduction.</div></div><div><h3>Methods</h3><div>Transcription datasets of SCI patients were acquired from Gene Expression Omnibus (GEO). Differentially expressed genes (DEGs) underwent functional enrichment analysis, and CIBERSORT assessed immune cell infiltration in SCI. Crucial lactylation-related differentially expressed genes (LRDEGs) associated with SCI were identified via machine learning. The association between LRDEGs and inflammatory response in SCI mediated by immune cell infiltration was confirmed using Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG). Rats with subacute thoracic SCI were transplanted with hUC-MSCs, and transcriptome analyses were conducted on their spinal cords and retrieved hUC-MSCs, respectively.</div></div><div><h3>Results</h3><div>The study identified 808 DEGs and 13 differentially infiltrated immune cell types in SCI patients compared to healthy controls. Multiple inflammatory response-related signaling pathways were activated in SCI. Seven LRDEGs, including LSP1, XRCC4, HSDL2, HNRNPH1, RPL14, IKZF1, and TP53, were recognized as key regulators. These genes are linked to immune cell infiltration and inflammatory responses in SCI. In SCI rats, the increased expression of LRDEGs and inflammatory cytokines were observed, which were significantly reduced after hUC-MSC transplantation. Differences in LRDEG expression patterns, enriched functions, and pathways between two SCI subtypes were statistically significant.</div></div><div><h3>Conclusions</h3><div>LRDEGs are involved in immune cell-mediated inflammatory response in SCI, and hUC-MSC transplantation reduces LRDEGs expression and inflammation response in the SCI microenvironment.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"191 ","pages":"Article 156960"},"PeriodicalIF":3.7,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143917577","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}
引用次数: 0
Association between frailty and inflammatory cytokines in patients with multiple sclerosis: a case-control study 多发性硬化症患者虚弱和炎症细胞因子之间的关系:一项病例对照研究
IF 3.7 3区 医学
Cytokine Pub Date : 2025-05-06 DOI: 10.1016/j.cyto.2025.156945
Shucheng Xing, Xue Li, Chen Chen
{"title":"Association between frailty and inflammatory cytokines in patients with multiple sclerosis: a case-control study","authors":"Shucheng Xing,&nbsp;Xue Li,&nbsp;Chen Chen","doi":"10.1016/j.cyto.2025.156945","DOIUrl":"10.1016/j.cyto.2025.156945","url":null,"abstract":"<div><h3>Background</h3><div>Frailty is a common symptom in Multiple Sclerosis (MS), yet its precise mechanism remains elusive, and the clinical implications of frailty in MS are uncertain. Moreover, inflammation is closely linked to frailty. This study aims to assess serum cytokine levels in individuals with MS and explore their correlation with frailty.</div></div><div><h3>Methods</h3><div>A case-control study included 83 primary MS patients and 100 healthy individuals undergoing health check-ups. Serum cytokine levels were measured, and MS severity was determined using the Expanded Disability Status Scale (EDSS) score. Additionally, a comprehensive frailty index (FI) was calculated based on health deficits from various domains following standardized procedures.</div></div><div><h3>Results</h3><div>Serum IL-6 and TNF-α levels were significantly higher in the frail group than in the non-frail group, with a statistically significant difference (<em>P</em> &lt; 0.05). After adjusting for disease duration, sex, age, BMI, SBP, and DBP, serum IL-6 independently correlated with frailty in MS patients (OR = 1.46; 95 % CI = 1.02–1.93; <em>P</em> = 0.003). Moreover, increased serum IL-6 levels were associated positively with the frailty index (β = 0.123, <em>P</em> = 0.008).</div></div><div><h3>Conclusion</h3><div>Our initial findings suggest elevated levels of pro-inflammatory cytokines in MS patients with frailty, with IL-6 showing a positive correlation with frail indices. These results underscore the potential impact of inflammatory responses on frailty development in MS.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"191 ","pages":"Article 156945"},"PeriodicalIF":3.7,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143906812","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}
引用次数: 0
Based on the IL-33/ST2-MyD88 signaling pathway to explore the mechanism of aerobic exercise in antagonizing the inflammatory response in depressive mice 基于IL-33/ST2-MyD88信号通路,探讨有氧运动对抗抑郁小鼠炎症反应的机制
IF 3.7 3区 医学
Cytokine Pub Date : 2025-05-03 DOI: 10.1016/j.cyto.2025.156956
Lei Gao , Ruilian Liu , He Qu , Honglin Qu , Qingyun Bai , Yilin Chen
{"title":"Based on the IL-33/ST2-MyD88 signaling pathway to explore the mechanism of aerobic exercise in antagonizing the inflammatory response in depressive mice","authors":"Lei Gao ,&nbsp;Ruilian Liu ,&nbsp;He Qu ,&nbsp;Honglin Qu ,&nbsp;Qingyun Bai ,&nbsp;Yilin Chen","doi":"10.1016/j.cyto.2025.156956","DOIUrl":"10.1016/j.cyto.2025.156956","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Purpose&lt;/h3&gt;&lt;div&gt;This study examined how aerobic exercise affect the IL-33/ST2-MyD88 signaling pathway in mice with chronic unpredictable mild stress (CUMS) induced depression&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Method&lt;/h3&gt;&lt;div&gt;Thirty-six C57BL/6 mice were randomly assigned t three groups: a control group (CG), a model group (MG), and an exercise group (ME). We created a depression model using chronic unpredictable mild stress, after which the ME group underwent 8 weeks of aerobic training. After exercise intervention, neurobehavioral assessment was performed. ELISA was used to detect the levels of IL-33, IL-1β and IL-10 in the serum of mice. Toluidine blue Nissl staining was used to observe the structure of hippocampal neurons. Total RNA was extracted from blood samples using magnetic beads and from hippocampal tissue or neurons using Trizol. The levels of IL-33, ST2, MyD88, IL-1β, IL-10 and NF-κB mRNA in mice were detected by RT-PCR&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Result&lt;/h3&gt;&lt;div&gt;The number of lattice crossings and modification times were significantly reduced in MG group, the exercise time was significantly shortened, and the sugar and water preference index was significantly reduced, while the immobility time in forced swimming and tail suspension tests were significantly prolonged. The results indicated that CUMS successfully induced anhedonia and depression-like behaviors in the mice. In the ME group, there was a significant increase in the number of crossing lattices, modification times, exercise duration, and sugar and water preference index, while the immobility time in the forced swimming and tail suspension tests significantly decreased. Compared with the CG group, serum levels of inflammatory factors IL-33, IL-1β, and NF-κB significantly increased in the MG group, while these levels significantly decreased in the ME group. It decreased and IL-10 showed a very significant increase. Nissl staining results indicated that hippocampal nerve cells in MG group were sparsely arranged, with widened gaps, severe nucleus contraction, and shallow staining. The ME group had reduced neuronal vacuoles and improved nuclear shrinkage. Immunohistochemical results revealed that in MG group, the expression of pro-inflammatory factors IL-1β and MyD88 increased. In Contrast, the ME group exhibited a decrease in IL-1β and MyD88, alongside a significant increase in the anti-inflammatory factor IL-10. In the RT-PCR test results, the blood inflammation signal pathway IL-33/ST2 and its downstream factors MyD88, NF-κB, and IL-1β mRNA were significantly up-regulated, and the inhibitory factor IL-10 mRNA was up-regulated in MG group. Gene expression trends for IL-33 mRNA, ST2 mRNA, IL-1β mRNA, MyD88 mRNA and NF-κB mRNA in hippocampus tissue were similar to those in blood, all showing significant up-regulation. In contrast, IL-10 mRNA did not exhibit significant up-regulation. While IL-33/ST2 expression did not significantly decrease, other pro-inflammatory factors showed significant","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"191 ","pages":"Article 156956"},"PeriodicalIF":3.7,"publicationDate":"2025-05-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143900055","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}
引用次数: 0
The role of interleukin (IL)-2 cytokine family in Parkinson's disease 白细胞介素-2细胞因子家族在帕金森病中的作用
IF 3.7 3区 医学
Cytokine Pub Date : 2025-05-02 DOI: 10.1016/j.cyto.2025.156954
Pouya Goleij , Alireza Amini , Mohammad Amin Khazeei Tabari , Mahboube Hadipour , Pantea Majma Sanaye , Khalaf F. Alsharif , Maria Daglia , Danaé S. Larsen , Haroon Khan
{"title":"The role of interleukin (IL)-2 cytokine family in Parkinson's disease","authors":"Pouya Goleij ,&nbsp;Alireza Amini ,&nbsp;Mohammad Amin Khazeei Tabari ,&nbsp;Mahboube Hadipour ,&nbsp;Pantea Majma Sanaye ,&nbsp;Khalaf F. Alsharif ,&nbsp;Maria Daglia ,&nbsp;Danaé S. Larsen ,&nbsp;Haroon Khan","doi":"10.1016/j.cyto.2025.156954","DOIUrl":"10.1016/j.cyto.2025.156954","url":null,"abstract":"<div><div>Parkinson's disease (PD) is a neurodegenerative disorder, which primarily impacts the nervous system, marked by its immune and inflammatory characteristics. The interleukin-2 (IL-2) cytokine family has a crucial role in regulating both neuroinflammation and immune activity, positioning it as one of the critical immune pathways in PD. Balancing pro-inflammatory and anti-inflammatory signals in PD heavily depends on the IL-2 cytokine family, that includes IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21. This balance is vital for neuron survival and resistance to degeneration. Disruptions in IL-2 signaling can upset the equilibrium among regulatory T cells (Tregs) and pro-inflammatory T cells, such as Th1 and Th17, further aggravating the chronic neuroinflammation typical of PD. In PD, a decline in IL-2 or receptor dysfunction can hinder Treg activity, leading to increased inflammation and neurodegeneration. Similarly, IL-15 and IL-21 supports cytotoxic immune cell function, including natural killer (NK) cells and CD8+ T cells, which may exacerbate neuronal damage by sustaining pro-inflammatory processes. Moreover, IL-4 and IL-7 have anti-inflammatory roles in maintaining T cell homeostasis, and their dysregulation can contribute to interruption of the blood-brain barrier and increased infiltration of immune cells into the central nervous system. Targeting the IL-2 cytokine family in Parkinson's disease has shown therapeutic potential by expanding Tregs, which reduce neuroinflammation and promote dopaminergic neuron survival. Recombinant IL-2 and IL-2/anti-IL-2 complexes have demonstrated efficacy in animal models, enhancing Treg function and leading to improved neuroprotection. Additionally, IL-4-based therapies have been explored for their ability to shift microglia toward a neuroprotective phenotype, further enhancing neuronal survival by modulating inflammatory responses and cellular metabolism. Current research is exploring how to optimize cytokine delivery while minimizing immune side effects, with the goal of developing more targeted therapies for PD.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"191 ","pages":"Article 156954"},"PeriodicalIF":3.7,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143900054","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}
引用次数: 0
Unraveling the immune activation mechanisms of DAMPs in coronary artery disease through transcriptomic and single-cell analyses 通过转录组学和单细胞分析揭示DAMPs在冠状动脉疾病中的免疫激活机制
IF 3.7 3区 医学
Cytokine Pub Date : 2025-04-28 DOI: 10.1016/j.cyto.2025.156952
Yinghao Li, Henghe Shi, Yifei Zou, Yinuo Guan, Ning Liu, Bin Liu
{"title":"Unraveling the immune activation mechanisms of DAMPs in coronary artery disease through transcriptomic and single-cell analyses","authors":"Yinghao Li,&nbsp;Henghe Shi,&nbsp;Yifei Zou,&nbsp;Yinuo Guan,&nbsp;Ning Liu,&nbsp;Bin Liu","doi":"10.1016/j.cyto.2025.156952","DOIUrl":"10.1016/j.cyto.2025.156952","url":null,"abstract":"<div><div>This study employs transcriptomics and single-cell analysis to delve into the mechanisms by which damage-associated molecular patterns (DAMPs) trigger immune activation in coronary artery disease (CAD). We obtained RNA-seq data from the GSE202625 and GSE242046 datasets, as well as single-cell RNA-seq data from the GSE159677 dataset, all sourced from the GEO database. Through differential expression analysis, we identified 821 differentially expressed genes (DEGs), comprising 389 upregulated and 432 downregulated genes, which are likely closely associated with the pathological processes of CAD. Notably, the genes P2RY14 and IFIH1 exhibited significant expression differences in CAD, suggesting their potential involvement in immune responses and inflammatory processes. Our findings indicate a significant infiltration and activation of immune cells in CAD patients, particularly T cells and macrophages. The activation of these cells is likely linked to the release of DAMPs and the activation of pattern recognition receptors (PRRs), thereby triggering local and systemic inflammatory responses. Single-cell analysis further revealed distinct clustering patterns of immune cells, especially T cells and B cells, in CAD patients compared to healthy controls. Dendritic cells and macrophages play particularly critical roles in the development of CAD. Dendritic cells bridge innate and adaptive immune responses by presenting antigens to T lymphocytes, potentially either promoting or inhibiting the progression of atherosclerosis. Macrophages exhibit polarization during the atherosclerosis process, with M1-type macrophages tending to promote inflammatory responses, while M2-type macrophages may exert anti-inflammatory effects.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"191 ","pages":"Article 156952"},"PeriodicalIF":3.7,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143882371","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}
引用次数: 0
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