HMGB1 released from pyroptotic vascular endothelial cells promotes immune disorders in exertional heatstroke.

IF 3 3区 医学 Q2 ONCOLOGY International Journal of Hyperthermia Pub Date : 2024-01-01 Epub Date: 2024-08-08 DOI:10.1080/02656736.2024.2378867
Chaoping Yu, Yang Huang, Jiangang Xie, Chujun Duan, Shanshou Liu, Wei Zhao, Yutong Wang, Ran Zhuang, Junjie Li, Wen Yin
{"title":"HMGB1 released from pyroptotic vascular endothelial cells promotes immune disorders in exertional heatstroke.","authors":"Chaoping Yu, Yang Huang, Jiangang Xie, Chujun Duan, Shanshou Liu, Wei Zhao, Yutong Wang, Ran Zhuang, Junjie Li, Wen Yin","doi":"10.1080/02656736.2024.2378867","DOIUrl":null,"url":null,"abstract":"<p><strong>Background and objective: </strong>Exertional heatstroke (EHS) mainly occurs in healthy young people with rapid onset and high mortality. EHS immune disorders can cause systemic inflammatory responses and multiple organ failure; however, the underlying mechanisms remain unclear. As high mobility group box 1 (HMGB1) is a prototypical alarmin that activates inflammatory and immune responses, this study aimed to investigate the effect and mechanism of HMGB1 in the pathogenesis of EHS.</p><p><strong>Methods: </strong>Peripheral blood mononuclear cell (PBMC) transcriptome sequencing of healthy volunteers, classical heatstroke patients, and EHS patients was performed. A mouse model of EHS was established and murine tissue damage was evaluated by H&E staining. HMGB1 localization and release were visualized using immunofluorescence staining. Human umbilical vein endothelial cells (HUVECs) and THP-1 cells were co-cultured to study the effects of HMGB1 on macrophages. A neutralizing anti-HMGB1 antibody was used to evaluate the efficacy of EHS treatment in mice.</p><p><strong>Results: </strong>Plasma and serum HMGB1 levels were significantly increased in EHS patients or mice. EHS-induced endothelial cell pyroptosis promoted HMGB1 release in mice. HMGB1 derived from endothelial cell pyroptosis enhanced macrophage pyroptosis, resulting in immune disorders under EHS conditions. Administration of anti-HMGB1 markedly alleviated tissue injury and systemic inflammatory responses after EHS.</p><p><strong>Conclusions: </strong>The release of HMGB1 from pyroptotic endothelial cells after EHS promotes pyroptosis of macrophages and systemic inflammatory response, and HMGB1-neutralizing antibody therapy has good application prospects for EHS.</p>","PeriodicalId":14137,"journal":{"name":"International Journal of Hyperthermia","volume":"41 1","pages":"2378867"},"PeriodicalIF":3.0000,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Hyperthermia","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1080/02656736.2024.2378867","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/8/8 0:00:00","PubModel":"Epub","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Background and objective: Exertional heatstroke (EHS) mainly occurs in healthy young people with rapid onset and high mortality. EHS immune disorders can cause systemic inflammatory responses and multiple organ failure; however, the underlying mechanisms remain unclear. As high mobility group box 1 (HMGB1) is a prototypical alarmin that activates inflammatory and immune responses, this study aimed to investigate the effect and mechanism of HMGB1 in the pathogenesis of EHS.

Methods: Peripheral blood mononuclear cell (PBMC) transcriptome sequencing of healthy volunteers, classical heatstroke patients, and EHS patients was performed. A mouse model of EHS was established and murine tissue damage was evaluated by H&E staining. HMGB1 localization and release were visualized using immunofluorescence staining. Human umbilical vein endothelial cells (HUVECs) and THP-1 cells were co-cultured to study the effects of HMGB1 on macrophages. A neutralizing anti-HMGB1 antibody was used to evaluate the efficacy of EHS treatment in mice.

Results: Plasma and serum HMGB1 levels were significantly increased in EHS patients or mice. EHS-induced endothelial cell pyroptosis promoted HMGB1 release in mice. HMGB1 derived from endothelial cell pyroptosis enhanced macrophage pyroptosis, resulting in immune disorders under EHS conditions. Administration of anti-HMGB1 markedly alleviated tissue injury and systemic inflammatory responses after EHS.

Conclusions: The release of HMGB1 from pyroptotic endothelial cells after EHS promotes pyroptosis of macrophages and systemic inflammatory response, and HMGB1-neutralizing antibody therapy has good application prospects for EHS.

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
发热血管内皮细胞释放的 HMGB1 会促进劳累性中暑的免疫紊乱。
背景和目的:劳累性中暑(EHS)主要发生在健康的年轻人身上,发病急、死亡率高。EHS 免疫紊乱可引起全身炎症反应和多器官功能衰竭;然而,其潜在机制仍不清楚。由于高迁移率基团框1(HMGB1)是激活炎症和免疫反应的典型警报蛋白,本研究旨在探讨HMGB1在EHS发病机制中的作用和机制:方法:对健康志愿者、典型中暑患者和 EHS 患者的外周血单核细胞(PBMC)转录组进行测序。建立了 EHS 小鼠模型,并通过 H&E 染色评估了小鼠组织损伤情况。采用免疫荧光染色法观察 HMGB1 的定位和释放情况。为了研究 HMGB1 对巨噬细胞的影响,研究人员将人脐静脉内皮细胞(HUVECs)和 THP-1 细胞进行了联合培养。使用中和抗 HMGB1 抗体评估 EHS 治疗小鼠的疗效:结果:EHS患者或小鼠血浆和血清中的HMGB1水平明显升高。EHS诱导的小鼠内皮细胞热解促进了HMGB1的释放。内皮细胞脓毒症产生的 HMGB1 增强了巨噬细胞的脓毒症,导致 EHS 条件下的免疫紊乱。服用抗 HMGB1 可明显减轻 EHS 后的组织损伤和全身炎症反应:结论:EHS后嗜热内皮细胞释放的HMGB1促进了巨噬细胞的嗜热和全身炎症反应,HMGB1中和抗体疗法在EHS中具有良好的应用前景。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
CiteScore
5.90
自引率
12.90%
发文量
153
审稿时长
6-12 weeks
期刊介绍: The International Journal of Hyperthermia
期刊最新文献
Therapeutic effects of focused ultrasound on vulvar squamous intraepithelial lesions in rat. Evaluation of the therapeutic efficacy of high-intensity focused ultrasound ablation combined with different drugs in the treatment of adenomyosis Heat shock protein-related diagnostic signature and molecular subtypes in ankylosing spondylitis: new pathogenesis insights Hyperthermia and cisplatin combination therapy promotes caspase-8 accumulation and activation to enhance apoptosis and pyroptosis in cancer cells Intravoxel incoherent motion (IVIM)-derived perfusion fraction mapping for the visual evaluation of MR-guided high intensity focused ultrasound (MR-HIFU) ablation of uterine fibroids
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1