来自骨髓增生异常综合征细胞的外泌体诱导巨噬细胞产生IL-1β，促进疾病进展

IF 3.7 3区医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY

Cytokine Pub Date : 2025-03-26 DOI:10.1016/j.cyto.2025.156924

Peichun Li , Dongmei Guan , Shuo Li , Ju Deng , HongYu Zhang , Xiaoli Liu , Xiuhua Chen , Zhifang Xu , Hongwei Wang , Fanggang Ren

{"title":"来自骨髓增生异常综合征细胞的外泌体诱导巨噬细胞产生IL-1β，促进疾病进展","authors":"Peichun Li , Dongmei Guan , Shuo Li , Ju Deng , HongYu Zhang , Xiaoli Liu , Xiuhua Chen , Zhifang Xu , Hongwei Wang , Fanggang Ren","doi":"10.1016/j.cyto.2025.156924","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><div>Exosomes are extracellular vesicles with a membrane structure that play important roles in intercellular communication, material transport and cellular immunity.Our previous study found that exosomes can affect the biological functions of MDS cell lines, but the mechanism of action has not been elucidated.Macrophages are one of the major innate immune cells that produce a variety of inflammatory cytokines and perform multiple biological functions in the tumor microenvironment (TME).The role of tumor cell-derived exosomes on macrophages and in the progression of MDS is rarely reported,therefore, the aim of our study was to investigate the effect of exosomes on macrophages and the effect of cytokines secreted by macrophages on MDS cells, with a view to exploring the role and mechanisms of exosomes and macrophages in the progression of MDS.</div></div><div><h3>Methods</h3><div>Changes in cytokine content in peripheral blood of MDS patients were detected. The cytokine concentration in the growth environment of MDS cell lines was changed to observe the changes in the biological functions of MDS cell lines.After induction of human monocyte cell line (THP-1) into THP-1-Mφ macrophages with Phorbol 12-myristate 13-acetate (PMA), the macrophages (Mφ) were then co-cultured with MDS cell line exosomes extracted by ultrafiltration with THP-1-Mφ to observe macrophage (Mφ) differentiation.Flow cytometry was used to detect the changes in cytokine content released by macrophages before and after the addition of exosome inhibitors, and the changes in the biological function of MDS cell lines during this process.Gene and protein levels of significantly changed cytokine-related signaling pathways were detected using Q-PCR and WB.</div></div><div><h3>Results</h3><div>IL-1β levels were significantly higher in the peripheral blood of MDS patients compared to controls.The exosomes extracted by ultrafiltration can be taken up by macrophages, which can promote the release of IL-1β from THP-1-Mφ cells, and promote the proliferation, apoptosis and migration ability of MDS cell lines.Exosomes stimulate macrophages to produce IL-1β and promote MDS disease progression through the MER/ERK pathway.</div></div>","PeriodicalId":297,"journal":{"name":"Cytokine","volume":"190 ","pages":"Article 156924"},"PeriodicalIF":3.7000,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Exosomes derived from myelodysplastic syndromes cells induce IL-1β production from macrophages to promote disease progress\",\"authors\":\"Peichun Li , Dongmei Guan , Shuo Li , Ju Deng , HongYu Zhang , Xiaoli Liu , Xiuhua Chen , Zhifang Xu , Hongwei Wang , Fanggang Ren\",\"doi\":\"10.1016/j.cyto.2025.156924\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><div>Exosomes are extracellular vesicles with a membrane structure that play important roles in intercellular communication, material transport and cellular immunity.Our previous study found that exosomes can affect the biological functions of MDS cell lines, but the mechanism of action has not been elucidated.Macrophages are one of the major innate immune cells that produce a variety of inflammatory cytokines and perform multiple biological functions in the tumor microenvironment (TME).The role of tumor cell-derived exosomes on macrophages and in the progression of MDS is rarely reported,therefore, the aim of our study was to investigate the effect of exosomes on macrophages and the effect of cytokines secreted by macrophages on MDS cells, with a view to exploring the role and mechanisms of exosomes and macrophages in the progression of MDS.</div></div><div><h3>Methods</h3><div>Changes in cytokine content in peripheral blood of MDS patients were detected. The cytokine concentration in the growth environment of MDS cell lines was changed to observe the changes in the biological functions of MDS cell lines.After induction of human monocyte cell line (THP-1) into THP-1-Mφ macrophages with Phorbol 12-myristate 13-acetate (PMA), the macrophages (Mφ) were then co-cultured with MDS cell line exosomes extracted by ultrafiltration with THP-1-Mφ to observe macrophage (Mφ) differentiation.Flow cytometry was used to detect the changes in cytokine content released by macrophages before and after the addition of exosome inhibitors, and the changes in the biological function of MDS cell lines during this process.Gene and protein levels of significantly changed cytokine-related signaling pathways were detected using Q-PCR and WB.</div></div><div><h3>Results</h3><div>IL-1β levels were significantly higher in the peripheral blood of MDS patients compared to controls.The exosomes extracted by ultrafiltration can be taken up by macrophages, which can promote the release of IL-1β from THP-1-Mφ cells, and promote the proliferation, apoptosis and migration ability of MDS cell lines.Exosomes stimulate macrophages to produce IL-1β and promote MDS disease progression through the MER/ERK pathway.</div></div>\",\"PeriodicalId\":297,\"journal\":{\"name\":\"Cytokine\",\"volume\":\"190 \",\"pages\":\"Article 156924\"},\"PeriodicalIF\":3.7000,\"publicationDate\":\"2025-03-26\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cytokine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1043466625000717\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cytokine","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1043466625000717","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}

引用次数: 0

摘要

小体是具有膜结构的细胞外囊泡，在细胞间通讯、物质运输和细胞免疫中起重要作用。我们前期研究发现外泌体可以影响MDS细胞系的生物学功能，但其作用机制尚未阐明。巨噬细胞是在肿瘤微环境（tumor microenvironment， TME）中产生多种炎性细胞因子并发挥多种生物学功能的主要先天免疫细胞之一。肿瘤细胞源性外泌体对巨噬细胞和MDS进展的作用鲜有报道，因此，我们的研究目的是研究外泌体对巨噬细胞的作用以及巨噬细胞分泌的细胞因子对MDS细胞的影响，以期探讨外泌体和巨噬细胞在MDS进展中的作用和机制。方法检测MDS患者外周血细胞因子含量的变化。通过改变MDS细胞系生长环境中的细胞因子浓度，观察MDS细胞系生物学功能的变化。将人单核细胞（THP-1）用Phorbol 12-肉豆酸酯13-乙酸酯（PMA）诱导成THP-1-Mφ巨噬细胞后，将巨噬细胞（Mφ）与THP-1-Mφ超滤提取的MDS细胞系外泌体共培养，观察巨噬细胞（Mφ）分化情况。采用流式细胞术检测添加外泌体抑制剂前后巨噬细胞释放的细胞因子含量的变化，以及此过程中MDS细胞系生物学功能的变化。采用Q-PCR和WB检测显著改变的细胞因子相关信号通路的基因和蛋白水平。结果MDS患者外周血sil -1β水平明显高于对照组。超滤提取的外泌体可被巨噬细胞摄取，可促进THP-1-Mφ细胞释放IL-1β，促进MDS细胞系的增殖、凋亡和迁移能力。外泌体刺激巨噬细胞产生IL-1β，并通过MER/ERK途径促进MDS疾病进展。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

Exosomes derived from myelodysplastic syndromes cells induce IL-1β production from macrophages to promote disease progress

查看原文本刊更多论文

Exosomes derived from myelodysplastic syndromes cells induce IL-1β production from macrophages to promote disease progress

Background

Exosomes are extracellular vesicles with a membrane structure that play important roles in intercellular communication, material transport and cellular immunity.Our previous study found that exosomes can affect the biological functions of MDS cell lines, but the mechanism of action has not been elucidated.Macrophages are one of the major innate immune cells that produce a variety of inflammatory cytokines and perform multiple biological functions in the tumor microenvironment (TME).The role of tumor cell-derived exosomes on macrophages and in the progression of MDS is rarely reported,therefore, the aim of our study was to investigate the effect of exosomes on macrophages and the effect of cytokines secreted by macrophages on MDS cells, with a view to exploring the role and mechanisms of exosomes and macrophages in the progression of MDS.

Methods

Changes in cytokine content in peripheral blood of MDS patients were detected. The cytokine concentration in the growth environment of MDS cell lines was changed to observe the changes in the biological functions of MDS cell lines.After induction of human monocyte cell line (THP-1) into THP-1-Mφ macrophages with Phorbol 12-myristate 13-acetate (PMA), the macrophages (Mφ) were then co-cultured with MDS cell line exosomes extracted by ultrafiltration with THP-1-Mφ to observe macrophage (Mφ) differentiation.Flow cytometry was used to detect the changes in cytokine content released by macrophages before and after the addition of exosome inhibitors, and the changes in the biological function of MDS cell lines during this process.Gene and protein levels of significantly changed cytokine-related signaling pathways were detected using Q-PCR and WB.

Results

IL-1β levels were significantly higher in the peripheral blood of MDS patients compared to controls.The exosomes extracted by ultrafiltration can be taken up by macrophages, which can promote the release of IL-1β from THP-1-Mφ cells, and promote the proliferation, apoptosis and migration ability of MDS cell lines.Exosomes stimulate macrophages to produce IL-1β and promote MDS disease progression through the MER/ERK pathway.

求助全文

通过发布文献求助，成功后即可免费获取论文全文。去求助

来源期刊

Cytokine 医学-免疫学

CiteScore

7.60

自引率

2.60%

发文量

262

审稿时长

48 days

期刊介绍： The journal Cytokine has an open access mirror journal Cytokine: X, sharing the same aims and scope, editorial team, submission system and rigorous peer review. * Devoted exclusively to the study of the molecular biology, genetics, biochemistry, immunology, genome-wide association studies, pathobiology, diagnostic and clinical applications of all known interleukins, hematopoietic factors, growth factors, cytotoxins, interferons, new cytokines, and chemokines, Cytokine provides comprehensive coverage of cytokines and their mechanisms of actions, 12 times a year by publishing original high quality refereed scientific papers from prominent investigators in both the academic and industrial sectors. We will publish 3 major types of manuscripts: 1) Original manuscripts describing research results. 2) Basic and clinical reviews describing cytokine actions and regulation. 3) Short commentaries/perspectives on recently published aspects of cytokines, pathogenesis and clinical results.