Ke Jin, Dan Zhao, Jun Zhou, Xun Zhang, Yujue Wang, Zhao Wu
{"title":"脉冲电磁场可抑制 IL-37,从而缓解 CD8+ T 细胞功能障碍并抑制宫颈癌的进展。","authors":"Ke Jin, Dan Zhao, Jun Zhou, Xun Zhang, Yujue Wang, Zhao Wu","doi":"10.1007/s10495-024-02006-8","DOIUrl":null,"url":null,"abstract":"<div><p>Pulsed electromagnetic field (PEMF) therapy is a potential non-invasive treatment to modulate immune responses and inhibit tumor growth. Cervical cancer (CC) is influenced by IL-37-mediated immune regulation, making PEMF therapy a potential strategy to impede CC progression. This study aimed to elucidate the effects of PEMF on IL-37 regulation and its molecular mechanisms in CC. CC cell-xenografted mouse models, including IL-37 transgenic (IL-37tg) mice, were used to assess tumor growth through in vivo fluorescence imaging and analyze CC cell apoptosis <i>via</i> flow cytometry. TCGA-CESC transcriptome and clinical data were analyzed to identify key inflammation and immune-related genes. CD8<sup>+</sup> T cell models were stimulated with PEMF, and apoptosis, oxidative stress, and inflammatory factor expression were analyzed through RT-qPCR, Western blot, and flow cytometry. PEMF treatment significantly inhibited IL-37 expression (<i>p <</i> 0.05), promoted inflammatory factor release (TNF-α and IL-6), and activated oxidative stress, leading to increased CC cell apoptosis (<i>p <</i> 0.05). IL-37 interaction with SMAD3 impacted the p38/NF-κB signaling pathway, modulating CD8<sup>+</sup> T cell activity and cytotoxicity. Co-culture of Hela cells with CD8<sup>+</sup> T cells under PEMF treatment showed reduced proliferation (by 40%), migration, and invasion (<i>p <</i> 0.05). In vivo experiments with CC-bearing mice demonstrated that PEMF treatment downregulated IL-37 expression (<i>p <</i> 0.05), enhanced CD8<sup>+</sup> T cell function, and inhibited tumor growth (<i>p <</i> 0.05). These molecular mechanisms were validated through RT-qPCR, Western blot, and immunohistochemistry. Thus, PEMF therapy inhibits CC progression by downregulating IL-37 and improving CD8<sup>+</sup> T cell function <i>via</i> the SMAD3/p38/NF-κB signaling pathway.</p></div>","PeriodicalId":8062,"journal":{"name":"Apoptosis","volume":"29 11-12","pages":"2108 - 2127"},"PeriodicalIF":6.1000,"publicationDate":"2024-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Pulsed electromagnetic fields inhibit IL-37 to alleviate CD8+ T cell dysfunction and suppress cervical cancer progression\",\"authors\":\"Ke Jin, Dan Zhao, Jun Zhou, Xun Zhang, Yujue Wang, Zhao Wu\",\"doi\":\"10.1007/s10495-024-02006-8\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Pulsed electromagnetic field (PEMF) therapy is a potential non-invasive treatment to modulate immune responses and inhibit tumor growth. Cervical cancer (CC) is influenced by IL-37-mediated immune regulation, making PEMF therapy a potential strategy to impede CC progression. This study aimed to elucidate the effects of PEMF on IL-37 regulation and its molecular mechanisms in CC. CC cell-xenografted mouse models, including IL-37 transgenic (IL-37tg) mice, were used to assess tumor growth through in vivo fluorescence imaging and analyze CC cell apoptosis <i>via</i> flow cytometry. TCGA-CESC transcriptome and clinical data were analyzed to identify key inflammation and immune-related genes. CD8<sup>+</sup> T cell models were stimulated with PEMF, and apoptosis, oxidative stress, and inflammatory factor expression were analyzed through RT-qPCR, Western blot, and flow cytometry. PEMF treatment significantly inhibited IL-37 expression (<i>p <</i> 0.05), promoted inflammatory factor release (TNF-α and IL-6), and activated oxidative stress, leading to increased CC cell apoptosis (<i>p <</i> 0.05). IL-37 interaction with SMAD3 impacted the p38/NF-κB signaling pathway, modulating CD8<sup>+</sup> T cell activity and cytotoxicity. Co-culture of Hela cells with CD8<sup>+</sup> T cells under PEMF treatment showed reduced proliferation (by 40%), migration, and invasion (<i>p <</i> 0.05). In vivo experiments with CC-bearing mice demonstrated that PEMF treatment downregulated IL-37 expression (<i>p <</i> 0.05), enhanced CD8<sup>+</sup> T cell function, and inhibited tumor growth (<i>p <</i> 0.05). These molecular mechanisms were validated through RT-qPCR, Western blot, and immunohistochemistry. Thus, PEMF therapy inhibits CC progression by downregulating IL-37 and improving CD8<sup>+</sup> T cell function <i>via</i> the SMAD3/p38/NF-κB signaling pathway.</p></div>\",\"PeriodicalId\":8062,\"journal\":{\"name\":\"Apoptosis\",\"volume\":\"29 11-12\",\"pages\":\"2108 - 2127\"},\"PeriodicalIF\":6.1000,\"publicationDate\":\"2024-10-15\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Apoptosis\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://link.springer.com/article/10.1007/s10495-024-02006-8\",\"RegionNum\":2,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Apoptosis","FirstCategoryId":"99","ListUrlMain":"https://link.springer.com/article/10.1007/s10495-024-02006-8","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
脉冲电磁场疗法(PEMF)是一种潜在的非侵入性疗法,可调节免疫反应并抑制肿瘤生长。宫颈癌(CC)受IL-37介导的免疫调节的影响,这使得脉冲电磁场疗法成为阻碍CC进展的潜在策略。本研究旨在阐明PEMF对IL-37调控的影响及其在CC中的分子机制。研究使用CC细胞异种移植小鼠模型,包括IL-37转基因(IL-37tg)小鼠,通过体内荧光成像评估肿瘤生长情况,并通过流式细胞术分析CC细胞凋亡情况。分析了 TCGA-CESC 转录组和临床数据,以确定关键的炎症和免疫相关基因。用PEMF刺激CD8+ T细胞模型,并通过RT-qPCR、Western印迹和流式细胞术分析细胞凋亡、氧化应激和炎症因子的表达。PEMF能明显抑制IL-37的表达(p + T细胞活性和细胞毒性)。在 PEMF 处理下,Hela 细胞与 CD8+ T 细胞共培养,结果显示增殖(减少 40%)、迁移和侵袭(p + T 细胞功能)减少,并通过 SMAD3/p38/NF-κB 信号通路抑制肿瘤生长(p + T 细胞功能)。
Pulsed electromagnetic fields inhibit IL-37 to alleviate CD8+ T cell dysfunction and suppress cervical cancer progression
Pulsed electromagnetic field (PEMF) therapy is a potential non-invasive treatment to modulate immune responses and inhibit tumor growth. Cervical cancer (CC) is influenced by IL-37-mediated immune regulation, making PEMF therapy a potential strategy to impede CC progression. This study aimed to elucidate the effects of PEMF on IL-37 regulation and its molecular mechanisms in CC. CC cell-xenografted mouse models, including IL-37 transgenic (IL-37tg) mice, were used to assess tumor growth through in vivo fluorescence imaging and analyze CC cell apoptosis via flow cytometry. TCGA-CESC transcriptome and clinical data were analyzed to identify key inflammation and immune-related genes. CD8+ T cell models were stimulated with PEMF, and apoptosis, oxidative stress, and inflammatory factor expression were analyzed through RT-qPCR, Western blot, and flow cytometry. PEMF treatment significantly inhibited IL-37 expression (p < 0.05), promoted inflammatory factor release (TNF-α and IL-6), and activated oxidative stress, leading to increased CC cell apoptosis (p < 0.05). IL-37 interaction with SMAD3 impacted the p38/NF-κB signaling pathway, modulating CD8+ T cell activity and cytotoxicity. Co-culture of Hela cells with CD8+ T cells under PEMF treatment showed reduced proliferation (by 40%), migration, and invasion (p < 0.05). In vivo experiments with CC-bearing mice demonstrated that PEMF treatment downregulated IL-37 expression (p < 0.05), enhanced CD8+ T cell function, and inhibited tumor growth (p < 0.05). These molecular mechanisms were validated through RT-qPCR, Western blot, and immunohistochemistry. Thus, PEMF therapy inhibits CC progression by downregulating IL-37 and improving CD8+ T cell function via the SMAD3/p38/NF-κB signaling pathway.
期刊介绍:
Apoptosis, a monthly international peer-reviewed journal, focuses on the rapid publication of innovative investigations into programmed cell death. The journal aims to stimulate research on the mechanisms and role of apoptosis in various human diseases, such as cancer, autoimmune disease, viral infection, AIDS, cardiovascular disease, neurodegenerative disorders, osteoporosis, and aging. The Editor-In-Chief acknowledges the importance of advancing clinical therapies for apoptosis-related diseases. Apoptosis considers Original Articles, Reviews, Short Communications, Letters to the Editor, and Book Reviews for publication.