Cytokine最新文献_第4页

Ang-1 promotes tumorigenesis and mediates the anti-cancer effects of Artesunate on Choroidal melanoma via the regulation of Akt/mTOR signaling pathway Ang-1 通过调控 Akt/mTOR 信号通路促进肿瘤发生并介导青蒿琥酯对脉络膜黑色素瘤的抗癌作用

IF 3.7 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cytokine

Pub Date : 2024-09-27 DOI: 10.1016/j.cyto.2024.156771

The impact of Ang-1 on tumors remains a subject of contention, with its mechanism of action exhibiting complexity in the progression of diverse tumor types. Ang-1 has been shown to promote the progression of glioma, glioma, esophageal and human cervical cancer, whereas it exerts inhibitory effects on the growth of breast and colon cancer. However, the specific function of Ang-1 in CM has not been clarified. This research aims to explore the function of Ang-1 on CM and the underlying mechanism. WB and qPCR were utilized to measure the expression levels of different factors in CM cells. Clonogenic, CCK-8 and Transwell migration assay were used to probe CM cells’ proliferation and migration ability. Xenograft tumor model was used to testify the effect of Ang-1 and Artesunate (ART) on the growth of CM in vivo. We found Ang-1 promoted CM proliferation and migration, while it was inhibited by ART in vitro. Moreover, both ART treatment and Ang-1 knockdown had the effect of suppressing tumor growth in CM xenograft model. Mechanically, Ang-1 activated Akt/mTOR pathway and induced epithelial-mesenchymal transition (EMT) in CM cells. Furthermore, ART regulated Akt/mTOR pathway by decreasing the expression of Ang-1 in CM cells. Ang-1 promotes tumorigenesis of CM by regulating Akt/mTOR pathway, which can be inhibited by ART.

Ang-1 对肿瘤的影响仍是一个争论不休的话题，其作用机制在不同类型肿瘤的发展过程中表现出复杂性。研究表明，Ang-1 能促进胶质瘤、神经胶质瘤、食管癌和人类宫颈癌的进展，而对乳腺癌和结肠癌的生长则有抑制作用。然而，Ang-1 在中医中的具体功能尚未明确。本研究旨在探索 Ang-1 对肿瘤的功能及其内在机制。本研究采用 WB 和 qPCR 方法测定不同因子在 CM 细胞中的表达水平。采用克隆、CCK-8和Transwell迁移试验检测CM细胞的增殖和迁移能力。利用异种移植肿瘤模型检验 Ang-1 和青蒿琥酯（ART）对体内 CM 生长的影响。我们发现 Ang-1 促进了 CM 的增殖和迁移，而 ART 则抑制了 CM 的增殖和迁移。此外，在 CM 异种移植模型中，ART 治疗和 Ang-1 基因敲除均有抑制肿瘤生长的作用。从机制上讲，Ang-1激活了Akt/mTOR通路，诱导了CM细胞的上皮-间质转化（EMT）。此外，ART通过降低Ang-1在CM细胞中的表达来调节Akt/mTOR通路。Ang-1通过调节Akt/mTOR通路促进CM的肿瘤发生，而Akt/mTOR通路可被ART抑制。

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引用次数: 0

Chemokines and chemokine receptors: Potential therapeutic targets in systemic lupus erythematosus 趋化因子和趋化因子受体：系统性红斑狼疮的潜在治疗目标

IF 3.7 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cytokine

Pub Date : 2024-09-25 DOI: 10.1016/j.cyto.2024.156770

Systemic lupus erythematosus (SLE) is an autoimmune disease that affects connective tissue and can lead to multisystem organ damage. Chemokines are a class of small proteins that interact with receptors and participate in a variety of physiological functions, including cell growth, differentiation, apoptosis and distribution. They also play important roles in pathological processes, such as the inflammatory response, wound repair, tumor formation and metastasis. Previous studies have shown that the levels of chemokines and their receptors are elevated in the blood and inflamed tissues of SLE patients. In addition, chemokine ligand-receptor interactions control the recruitment of leukocytes into tissues, suggesting that chemokines and their receptors may be biomarkers and therapeutic targets for SLE. This review summarizes the causative role of chemokines and their receptors in SLE, as well as their clinical values and challenges as potential biomarkers and therapeutic targets.

系统性红斑狼疮（SLE）是一种影响结缔组织的自身免疫性疾病，可导致多系统器官损伤。趋化因子是一类与受体相互作用的小蛋白，参与多种生理功能，包括细胞生长、分化、凋亡和分布。它们还在炎症反应、伤口修复、肿瘤形成和转移等病理过程中发挥重要作用。以往的研究表明，系统性红斑狼疮患者血液和炎症组织中的趋化因子及其受体水平升高。此外，趋化因子配体与受体之间的相互作用控制着白细胞向组织的募集，这表明趋化因子及其受体可能是系统性红斑狼疮的生物标志物和治疗靶点。本综述总结了趋化因子及其受体在系统性红斑狼疮中的致病作用，以及它们作为潜在生物标志物和治疗靶点的临床价值和挑战。

引用次数: 0

The role of cellular senescence in the pathogenesis of Rheumatoid Arthritis: Focus on IL-6 as a target gene 细胞衰老在类风湿关节炎发病机制中的作用：关注作为靶基因的 IL-6

IF 3.7 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cytokine

Pub Date : 2024-09-25 DOI: 10.1016/j.cyto.2024.156762

Background

Rheumatoid arthritis is a chronic autoimmune disease. However, the specific role of senescence in rheumatoid arthritis (RA) is unknown. This study aimed to identify potential aging-related genes that have diagnostic and therapeutic value for RA.

Methods

The GSE89408 dataset was downloaded from the Gene Expression Omnibus (GEO). Aging-related genes were downloaded from the HAGR database. Differentially expressed genes (DEGs) were subsequently identified with the “edgeR” tool. Next, hub genes were identified with a PPI network and CytoHubba analysis. Receiver operating characteristic (ROC) curves were used to evaluate the diagnostic value of these hub genes. Immune infiltration analysis was performed with the CIBERSORT algorithm. Additionally, molecular docking was performed with CB-Dock2. Finally, correlation experiments were performed to validate the bioinformatics and molecular docking results.

Results

A total of 22 ADEGs were identified. Combined PPI network and CytoHubba analyses identified a total of 7 hub genes, including IL-6, IL7R, IL2RG, CDK1, PTGS2, and LEP, which are associated mainly with inflammation and immune responses. ROC analysis revealed that the hub genes were highly predictive of RA. Analysis of immune infiltration revealed that the 6 hub genes were positively associated with M1 macrophages. Validation experiments revealed that the inhibition of IL-6 significantly decreased the degree of synovial fibroblast (FLS) senescence. Furthermore, molecular docking and validation experiments revealed that IL-6 is a potential target for drug therapy.

Conclusion

This study demonstrated that RA-FLS senescence may promote the development of RA via inflammatory and immune mechanisms. Seven hub genes were identified, of which IL-6 is a reliable biomarker for the diagnosis and treatment of RA.

背景类风湿性关节炎是一种慢性自身免疫性疾病。然而，衰老在类风湿性关节炎（RA）中的具体作用尚不清楚。本研究旨在鉴定对类风湿关节炎有诊断和治疗价值的潜在衰老相关基因。方法从基因表达总库（GEO）下载 GSE89408 数据集。衰老相关基因从 HAGR 数据库下载。随后使用 "edgeR "工具鉴定了差异表达基因（DEGs）。接着，通过 PPI 网络和 CytoHubba 分析确定了枢纽基因。接收者操作特征曲线（ROC）用于评估这些中心基因的诊断价值。利用 CIBERSORT 算法进行了免疫浸润分析。此外，还使用 CB-Dock2 进行了分子对接。最后，进行了相关实验来验证生物信息学和分子对接的结果。结合 PPI 网络和 CytoHubba 分析，共发现了 7 个枢纽基因，包括 IL-6、IL7R、IL2RG、CDK1、PTGS2 和 LEP，它们主要与炎症和免疫反应有关。ROC分析显示，这些中枢基因对RA具有高度预测性。免疫浸润分析显示，6个中心基因与M1巨噬细胞呈正相关。验证实验显示，抑制IL-6可显著降低滑膜成纤维细胞（FLS）的衰老程度。此外，分子对接和验证实验显示，IL-6是药物治疗的潜在靶点。本研究发现了七个枢纽基因，其中 IL-6 是诊断和治疗 RA 的可靠生物标志物。

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引用次数: 0

The assessment of usefulness of cytokines and other soluble mediators as the predictors of sequalae development in various forms of tick-borne encephalitis (TBE) 评估细胞因子和其他可溶性介质作为各种蜱传脑炎（TBE）后遗症发展预测因子的作用

IF 3.7 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cytokine

Pub Date : 2024-09-25 DOI: 10.1016/j.cyto.2024.156767

Aim

The aim of the study was to assess the usefulness of cytokines and other soluble mediators in differentiation between severe and mild course of tick-borne encephalitis (TBE) as well as the predictor of sequalae development.

Material and methods

122 patients (mean age 47.66 ± 14.77 years, 43 females, 79 males) with TBE were included in the study.

Concentrations of 82 cytokines, growth factors, selectins, matrix metalloproteinases and other soluble mediators were measured in serum and CSF samples according to the manufacturer’s instruction on a Bio-Plex 200 System using the custom made Luminex assays. Enzyme-linked immunosorbent assays for the quantitative detection of human IL-26, IL-29 IL-22, CXCL12 were performed.

Results

No significant differences between serum concentrations of examined factors between group with sequelae and group with complete recovery were observed.

In the CSF the concentrations of GM-CSF, Il-1α, Il-2, Il-4, Il-6, Il-12p70, Il-17A, CXCL1, CXCL6, Il-8, CCL4, CCL20, TRAIL, CD40L, MMP8 were significantly higher in patients who developed sequelae than in patients with complete recovery.

For TRAIL concentration over 26.65 pg/ml in CSF the probability of sequalae development was 10.5 higher. In case of CCL20 – the concentration over 21.38 pg/ml in CSF the odds ratio was 6.429 times. For MMP-8 over 4210.54 pg/ml, the odds ratio was 11.222 times.

Conclusions

TRAIL, CCL-20 and MMP-8 are promising biomarkers of prediction of the sequalae development of TBE.

Pro-inflammatory cytokines IL-8, IL-1, IL-2, IL-12, IL-17A also associate well with the risk of sequelae and could be further evaluated as prognostic markers in TBE, individually or as elements of a larger model.

研究旨在评估细胞因子和其他可溶性介质在区分蜱传脑炎（TBE）重度和轻度病程中的作用，以及预测后遗症发展的作用。血清和脑脊液样本中 82 种细胞因子、生长因子、选择素、基质金属蛋白酶和其他可溶性介质的浓度均按照制造商的说明在 Bio-Plex 200 系统上使用定制的 Luminex 分析方法进行了测定。结果后遗症组和完全康复组血清中被检因子的浓度无明显差异。在脑脊液中，后遗症患者的 GM-CSF、Il-1α、Il-2、Il-4、Il-6、Il-12p70、Il-17A、CXCL1、CXCL6、Il-8、CCL4、CCL20、TRAIL、CD40L、MMP8 的浓度明显高于完全康复患者。CCL20--CSF中浓度超过21.38 pg/ml的几率比为6.429倍。结论TRAIL、CCL-20 和 MMP-8 是预测肺结核后遗症发生的有希望的生物标志物。前炎症细胞因子 IL-8、IL-1、IL-2、IL-12、IL-17A 也与后遗症风险密切相关，可作为肺结核的预后标志物单独或作为更大模型的元素进行进一步评估。

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引用次数: 0

Skin wound repairing effects of adipose mesenchymal stem cells is promoted by the combined application of insulin-like growth factor 1: The key role of miR-21-5p-mediated signaling transduction 联合应用胰岛素样生长因子1促进脂肪间充质干细胞的皮肤伤口修复效应：miR-21-5p介导的信号转导的关键作用

IF 3.7 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cytokine

Pub Date : 2024-09-23 DOI: 10.1016/j.cyto.2024.156760

Mesenchymal stem cells (ADMSCs) have been applied to the treatment of skin injuries and the co-administration of cytokines can enhance the effects. In the current study, the promoting effects of insulin-like growth factor 1 (IGF-1) on the skin wound healing effects of adipose-derived MSCs (ADMSCs) were assessed and the associated mechanism was explored by focusing on miR-21-5p mediated pathways. ADMSCs were isolated from epididymis rats, and skin wounded rats were employed as the in vivo model for evaluating the effect of ADMCs on skin healing and secretion of cytokines. Then a microarray assay was employed to select potential miR target of IGF-1 on ADMSCs. The level of the selected miR was modulated in ADMSCs, and the effects on skin injuries were also assessed. Administration of ADMSCs promoted skin wound healing and induced the production of bFGF, IL-1β, PDGF, SDF-1, IGF-1, and TNF-α. The co-administration of IGF-1 and ADMSCs strengthened the effect of ADMSCs on skin wound by suppressing activity of matrix metalloproteinase-1 (MMP-1). At molecular level, the treatment of IGF-1 up-regulated miR-21-5p level in ADMSCs, which then suppressed the expression of KLF6 in injured skin tissues and promoted wound healing. The inhibition of miR-21-5p counteracted the promoting effects of IGF-1 on the skin healing effects of ADMSCs. Findings outlined in the current study indicated that IGF-1 could promote the wound healing effects of ADMSCs by up-regulating miR-21-5p level.

间充质干细胞（ADMSCs）已被应用于治疗皮肤损伤，联合使用细胞因子可增强其效果。本研究评估了胰岛素样生长因子1（IGF-1）对脂肪间充质干细胞（ADMSCs）皮肤伤口愈合效果的促进作用，并通过关注miR-21-5p介导的途径探讨了相关机制。研究人员从附睾大鼠体内分离出 ADMSCs，并以皮肤损伤大鼠为体内模型，评估 ADMCs 对皮肤愈合和细胞因子分泌的影响。然后用芯片分析法筛选出 IGF-1 在 ADMSCs 上的潜在 miR 靶标。研究人员调节了所选 miR 在 ADMSCs 中的水平，并评估了其对皮肤损伤的影响。给予 ADMSCs 可促进皮肤伤口愈合，并诱导产生 bFGF、IL-1β、PDGF、SDF-1、IGF-1 和 TNF-α。通过抑制基质金属蛋白酶-1（MMP-1）的活性，IGF-1 和 ADMSCs 的联合应用加强了 ADMSCs 对皮肤伤口的作用。在分子水平上，IGF-1能上调ADMSCs中的miR-21-5p水平，进而抑制KLF6在受伤皮肤组织中的表达，促进伤口愈合。抑制 miR-21-5p 可抵消 IGF-1 对 ADMSCs 皮肤愈合作用的促进作用。本研究概述的结果表明，IGF-1 可通过上调 miR-21-5p 水平促进 ADMSCs 的伤口愈合作用。

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引用次数: 0

Zinc pathogenic importance in correcting immunity and restoring public health in the post-COVID period: An overview 锌致病剂在后 COVID 时期纠正免疫和恢复公众健康方面的重要性：概述

IF 3.7 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cytokine

Pub Date : 2024-09-21 DOI: 10.1016/j.cyto.2024.156761

Context: The problem of correcting immune system function and compensating for co-morbidities becomes particularly clinically significant in the post-COVID period. There is evidence that certain trace elements in the human body, particularly zinc ions, play a critical role in restoring the function of the immune system and internal organs. Objective: To analyze the mechanisms of zinc action maintaining the body homeostasis in order to justify pathogenetically the inclusion of zinc drugs in the therapy of patients in the post-COVID period. Methods: Data from Elsevier, Global Health, PubMed-NCBI, Embase, MEDLINE, Scopus, Research gate, RSCI Scopus, Cochrane Library, Google Academy, e-LIBRARY.RU and CyberLeninka were used. Results: This review showed that the importance of zinc in maintaining body homeostasis in the post-COVID period is determined by its multifaceted effect on all parts of the immune system, its anti-inflammatory activity, antimicrobial properties and participation in the restoration of internal organ function. Elimination of zinc deficiency in the post-COVID period is essential to support immunity, compensate for comorbidities and reduce the risk of complications. The impossibility of synthesizing zinc in the body requires its constant intake in sufficient quantities. Zinc levels are significantly reduced after infectious diseases, as this element is specifically distributed to organs and tissues to maintain immunological and metabolic functions. The degree of zinc deficiency is associated with the severity of COVID-19 and the post-COVID period. It is pathogenetically justified to prescribe zinc drugs in the post-COVID period, the choice of which should take into account comorbidities and severity of hypozincemia. Conclusion: Regularly administered therapy with zinc drugs in the post-COVID period will help correct the population immunity and restore public health.

背景：在后 COVID 期，纠正免疫系统功能和补偿并发症的问题在临床上变得尤为重要。有证据表明，人体内的某些微量元素，尤其是锌离子，在恢复免疫系统和内脏器官功能方面发挥着至关重要的作用。研究目的分析锌在维持机体平衡方面的作用机制，以便从病理学角度证明将锌药物纳入后 COVID 期患者的治疗中是合理的。研究方法数据来源：Elsevier、Global Health、PubMed-NCBI、Embase、MEDLINE、Scopus、Research gate、RSCI Scopus、Cochrane Library、Google Academy、e-LIBRARY.RU 和 CyberLeninka。结果综述显示，锌对免疫系统各部分的多方面影响、抗炎活性、抗菌特性以及参与内脏器官功能的恢复，决定了锌在 COVID 后时期维持机体平衡的重要性。在后 COVID 期间消除锌缺乏症对于支持免疫力、补偿并发症和降低并发症风险至关重要。由于体内无法合成锌，因此需要不断摄入足量的锌。感染性疾病后，体内的锌含量会明显降低，因为这种元素专门分布在器官和组织中，以维持免疫和新陈代谢功能。缺锌的程度与 COVID-19 的严重程度和 COVID 后的时期有关。从病理学角度来看，在 COVID 后时期处方锌药物是合理的，但在选择药物时应考虑到合并症和低锌血症的严重程度。结论在禽流感后时期定期使用锌药物治疗将有助于纠正人群免疫力和恢复公众健康。

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引用次数: 0

Associations between per- and poly-fluoroalkyl substance (PFAS) exposure and immune responses among women in the California Teachers study: A cross-sectional evaluation 加利福尼亚教师研究中女性接触全氟和多氟烷基物质 (PFAS) 与免疫反应之间的关系：横断面评估

IF 3.7 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cytokine

Pub Date : 2024-09-18 DOI: 10.1016/j.cyto.2024.156753

Introduction

Per- and polyfluoroalkyl substances (PFAS) are persistent environmental contaminants that have been linked to a number of health outcomes, including those related to immune dysfunction. However, there are limited numbers of epidemiological-based studies that directly examine the association between PFAS exposure and immune responses.

Methods

In this cross-sectional study nested in the California Teachers Study cohort, we measured nine PFAS analytes in serum. Of the 9 analytes, we further evaluated four (PFHxS [perfluorohexane sulfonate], PFNA [perfluorononanoic acid], PFOA [perfluorooctanoic acid], PFOS [perfluorooctanesulfonic acid]) that had detection levels of > 80 %, in relation to 16 systemic inflammatory/immune markers and corresponding immune pathways (Th1 [pro-inflammatory/macrophage activation], B-cell activation, and T-cell activation). Study participants (n = 722) were female, completed a questionnaire regarding various health measures and behaviors, and donated a blood sample between 2013–2016. The association between PFAS analytes and individual immune markers and pathways were evaluated by calculating odds ratios (OR) and 95 % confidence intervals (CI) in a logistic regression model. PFAS analytes were evaluated both as a dichotomous exposure (above or below the respective median) and as a continuous variable (per 1 unit increase [ng/mL]).

Results

The prevalence of detecting any PFAS analyte rose with increasing age, with the highest PFAS prevalence observed among those aged 75 + years and the lowest PFAS prevalence observed among those aged 40–49 years (study participant age range: 40–95 years). Significant associations with BAFF (B-cell activating factor) levels above the median were observed among participants with elevated (defined as above the median) levels of PFHxS (OR=1.53), PFOA (OR=1.43), and PFOS (OR=1.40). Similarly, there were statistically significant associations between elevated levels of PFHxS and TNFRII (tumor necrosis factor receptor 2) levels (OR=1.78) and IL2Rα (interleukin 2 receptor subunit alpha) levels (OR=1.48). We also observed significant inverse associations between elevated PFNA and sCD14 (soluble cluster of differentiation 14) (OR=0.73). No significant associations were observed between elevated PFNA and any immune marker. Evaluation of PFAS exposures as continuous exposures in association with dichotomized cytokines were generally consistent with the dichotomized associations.

Conclusions

PFAS exposure was associated with altered levels of circulating inflammatory/immune markers; the associations were specific to PFAS analyte and immune marker. If validated, our results may suggest potential immune mechanisms underlying associations between the different PFAS analytes and adverse health outcomes.

引言全氟和多氟烷基物质（PFAS）是一种持久性环境污染物，与许多健康结果有关，包括与免疫功能障碍有关的健康结果。方法在这项嵌套于加州教师研究队列的横断面研究中，我们测量了血清中的九种全氟辛烷磺酸分析物。在这 9 种分析物中，我们进一步评估了 4 种（PFHxS [全氟己烷磺酸]、PFNA [全氟壬酸]、PFOA [全氟辛酸]、PFOS [全氟辛烷磺酸]）与 16 种全身炎症/免疫标记物和相应免疫途径（Th1 [促炎症/巨噬细胞活化]、B 细胞活化和 T 细胞活化）的关系，这些标记物的检测水平为 80%。研究参与者（n = 722）均为女性，填写了有关各种健康措施和行为的问卷，并在 2013-2016 年间捐献了血液样本。通过在逻辑回归模型中计算几率比（OR）和 95 % 置信区间（CI），评估了 PFAS 分析物与单个免疫标记物和免疫途径之间的关联。PFAS分析物既作为二分暴露量（高于或低于各自的中位数），也作为连续变量（每增加1个单位[纳克/毫升]）进行评估。结果检测到任何PFAS分析物的流行率随着年龄的增加而上升，75岁以上人群的PFAS流行率最高，40-49岁人群的PFAS流行率最低（研究参与者年龄范围：40-95岁）。在 PFHxS（OR=1.53）、PFOA（OR=1.43）和 PFOS（OR=1.40）水平升高（定义为高于中位数）的参与者中，观察到与 BAFF（B 细胞活化因子）水平高于中位数有显著关联。同样，PFHxS 水平升高与 TNFRII（肿瘤坏死因子受体 2）水平（OR=1.78）和 IL2Rα（白细胞介素 2 受体亚基 alpha）水平（OR=1.48）之间也存在统计学意义上的显著关联。我们还观察到 PFNA 升高与 sCD14（可溶性分化簇 14）之间存在明显的反向关系（OR=0.73）。未观察到 PFNA 升高与任何免疫标记物之间存在明显关联。结论 PFAS 暴露与循环炎症/免疫标记物水平的改变有关；这种关联与 PFAS 分析物和免疫标记物有关。如果得到验证，我们的研究结果可能表明不同的全氟辛烷磺酸分析物与不良健康结果之间存在潜在的免疫机制。

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引用次数: 0

Old drug, new use: Recent advances for G-CSF 老药新用：G-CSF 的最新进展

IF 3.7 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cytokine

Pub Date : 2024-09-17 DOI: 10.1016/j.cyto.2024.156759

Granulocyte colony-stimulating factor (G-CSF), also known as colony-stimulating factor 3 (CSF3), is a proinflammatory cytokine that primarily stimulates the survival, proliferation, differentiation and function of neutrophil granulocyte progenitor cells and mature neutrophils. Over the past years, G-CSF has mainly been used to cure patients with neutropenia and as a part of chemotherapy to induct the remission for refractory/relapse leukemia. Recent studies showed that C-CSF can been used as condition regimens and as a part of preventive methods after allogeneic transplantation to improve the survival of patients and also has immunoregulation, and has promote or inhibit the proliferation of solid tumors. Therefore, in this review, we firstly describe the structure for G-CSF. Then its functions and mechanism were reviewed including the neutrophil mobilization, differentiation, migration, and inhibiting apoptosis of neutrophils, and its immunoregulation. Finally, the clinical applications were further discussed.

粒细胞集落刺激因子（G-CSF）又称集落刺激因子 3（CSF3），是一种促炎细胞因子，主要刺激中性粒细胞祖细胞和成熟中性粒细胞的存活、增殖、分化和功能。多年来，G-CSF 主要用于治疗中性粒细胞减少症患者，并作为化疗的一部分，诱导难治性/复发性白血病患者病情缓解。最近的研究表明，C-CSF 可作为同种异体移植后的条件疗法和预防方法的一部分，以提高患者的生存率，同时还具有免疫调节作用，并能促进或抑制实体瘤的增殖。因此，在这篇综述中，我们首先描述了 G-CSF 的结构。然后综述了其功能和机制，包括中性粒细胞动员、分化、迁移、抑制中性粒细胞凋亡以及免疫调节。最后，进一步讨论了其临床应用。

引用次数: 0

IL-33/ST2 enhances MMP-12 expression by macrophages to mediate inflammatory and immune response in IgG4-Related Ophthalmic Disease IL-33/ST2 可增强巨噬细胞 MMP-12 的表达，从而介导 IgG4 相关眼病的炎症和免疫反应

IF 3.7 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cytokine

Pub Date : 2024-09-17 DOI: 10.1016/j.cyto.2024.156754

IgG4-Related Ophthalmic Disease (IgG4-ROD) is a chronic autoimmune-mediated fibrotic disease that predominantly affects the lacrimal glands, often leading to loss of function in the involved tissues or organs. Recent studies have demonstrated that MMP-12 is highly expressed in IgG4-ROD and plays a significant role in regulating immune responses. In this study, we reviewed nine patients diagnosed with IgG4-ROD based on clinical manifestations and histological analysis, and we investigated the expression of IL-33/ST2 and MMP-12 in IgG4-ROD lacrimal gland tissues using IHC. We found that IL-33 interacts with its specific receptor ST2, both of which are significantly overexpressed in IgG4-ROD tissues. Additionally, we successfully constructed a mouse model by introducing the Lat^Y136F mutation into C57BL/6 mice to mimic IgG4-ROD lacrimal gland involvement, which helped elucidate the mechanisms involved in the induction of MMP-12. Furthermore, immunofluorescence staining confirmed that most MMP-12⁺ cells were derived from M2 macrophages, and an ELISA assay demonstrated that IL-33 upregulates MMP-12 in IgG4-ROD. Collectively, these data suggest that the IL-33/ST2/MMP-12 signaling pathway is activated in IgG4-ROD, with IL-33/ST2 potentially promoting M2 macrophage polarization and activation to produce MMP-12, which may serve as a novel therapeutic target for IgG4-ROD.

IgG4 相关眼病（IgG4-ROD）是一种由自身免疫介导的慢性纤维化疾病，主要影响泪腺，往往导致受累组织或器官功能丧失。最近的研究表明，MMP-12 在 IgG4-ROD 中高度表达，并在调节免疫反应中发挥重要作用。在本研究中，我们回顾了根据临床表现和组织学分析确诊的9例IgG4-ROD患者，并使用IHC检测了IgG4-ROD泪腺组织中IL-33/ST2和MMP-12的表达。我们发现，IL-33与其特异性受体ST2相互作用，两者在IgG4-ROD组织中均显著过表达。此外，我们还通过在 C57BL/6 小鼠中引入 LatY136F 突变成功构建了一个小鼠模型，以模拟 IgG4-ROD 泪腺受累，这有助于阐明诱导 MMP-12 的相关机制。此外，免疫荧光染色证实，大多数MMP-12+细胞来自M2巨噬细胞，ELISA测定证明，IL-33能上调IgG4-ROD的MMP-12。总之，这些数据表明，IL-33/ST2/MMP-12信号通路在IgG4-ROD中被激活，IL-33/ST2可能促进M2巨噬细胞极化和活化以产生MMP-12，这可能成为IgG4-ROD的一个新的治疗靶点。

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引用次数: 0

Optimizing CAR-T cell Culture: Differential effects of IL-2, IL-12, and IL-21 on CAR-T cells 优化 CAR-T 细胞培养：IL-2、IL-12 和 IL-21 对 CAR-T 细胞的不同影响

IF 3.7 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cytokine

Pub Date : 2024-09-17 DOI: 10.1016/j.cyto.2024.156758

Background

Chimeric antigen receptor (CAR)-T therapy has demonstrated sustained clinical remission in numerous hematologic malignancies and has expanded to encompass solid tumors and autoimmune diseases. While progress is being made in establishing optimal culture conditions for CAR-T cells, the identification of the most effective cytokine for promoting their persistence in vitro remains elusive.

Methods

Here, we employed scRNA-seq (single-cell RNA sequencing) analysis to investigate the potential alterations in biological processes within CAR-T cells following exposure to cytokines (IL-2, IL-12, and IL-21) and antigens. Transcriptomic changes in diverse CAR-T groups were compared following various treatments, with a focus on epigenetic modifications, metabolic shifts, cellular senescence, and exhaustion.

Results

Our study reveals that CAR-T cells treated with antigen, IL-2, and IL-12 exhibit signs of exhaustion and senescence, whereas those treated with IL-21 do not display these characteristics. The activities of glycolysis and epigenetic changes were significantly increased by treatments with antigens, IL-2, and IL-12, while IL-21 treatment maintained the oxidative phosphorylation (OXPHOS) of CAR-T cells.

Conclusions

Our findings suggest that IL-21 may play a role in preventing senescence and could be utilized in combination with other strategies, such as IL-2 and IL-12, for CAR-T culture.

背景嵌合抗原受体（CAR）-T疗法已在多种血液系统恶性肿瘤中显示出持续的临床缓解效果，并已扩展到实体瘤和自身免疫性疾病。虽然在建立 CAR-T 细胞的最佳培养条件方面取得了进展，但确定促进其体外持续存在的最有效细胞因子的工作仍遥遥无期。方法在此，我们采用了 scRNA-seq（单细胞 RNA 测序）分析来研究暴露于细胞因子（IL-2、IL-12 和 IL-21）和抗原后 CAR-T 细胞内生物过程的潜在变化。结果我们的研究发现，接受抗原、IL-2 和 IL-12 处理的 CAR-T 细胞表现出衰竭和衰老的迹象，而接受 IL-21 处理的细胞则没有这些特征。糖酵解活性和表观遗传变化在抗原、IL-2 和 IL-12 的处理下显著增加，而 IL-21 处理则维持了 CAR-T 细胞的氧化磷酸化（OXPHOS）。

{"title":"Optimizing CAR-T cell Culture: Differential effects of IL-2, IL-12, and IL-21 on CAR-T cells","authors":"","doi":"10.1016/j.cyto.2024.156758","DOIUrl":"10.1016/j.cyto.2024.156758","url":null,"abstract":"<div><h3>Background</h3><p>Chimeric antigen receptor (CAR)-T therapy has demonstrated sustained clinical remission in numerous hematologic malignancies and has expanded to encompass solid tumors and autoimmune diseases. While progress is being made in establishing optimal culture conditions for CAR-T cells, the identification of the most effective cytokine for promoting their persistence in vitro remains elusive.</p></div><div><h3>Methods</h3><p>Here, we employed scRNA-seq (single-cell RNA sequencing) analysis to investigate the potential alterations in biological processes within CAR-T cells following exposure to cytokines (IL-2, IL-12, and IL-21) and antigens. Transcriptomic changes in diverse CAR-T groups were compared following various treatments, with a focus on epigenetic modifications, metabolic shifts, cellular senescence, and exhaustion.</p></div><div><h3>Results</h3><p>Our study reveals that CAR-T cells treated with antigen, IL-2, and IL-12 exhibit signs of exhaustion and senescence, whereas those treated with IL-21 do not display these characteristics. The activities of glycolysis and epigenetic changes were significantly increased by treatments with antigens, IL-2, and IL-12, while IL-21 treatment maintained the oxidative phosphorylation (OXPHOS) of CAR-T cells.</p></div><div><h3>Conclusions</h3><p>Our findings suggest that IL-21 may play a role in preventing senescence and could be utilized in combination with other strategies, such as IL-2 and IL-12, for CAR-T culture.</p></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":null,"pages":null},"PeriodicalIF":3.7,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142239018","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}

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