人乳寡糖 3'sialyllactose 可减少小鼠低度炎症和动脉粥样硬化的发生。

IF 6.3 1区 医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL JCI insight Pub Date : 2024-11-08 DOI:10.1172/jci.insight.181329
Ariane R Pessentheiner, Nathanael J Spann, Chloe A Autran, Tae Gyu Oh, Kaare V Grunddal, Joanna Kc Coker, Chelsea D Painter, Bastian Ramms, Austin Wt Chiang, Chen-Yi Wang, Jason Hsiao, Yiwen Wang, Anthony Quach, Laela M Booshehri, Alexandra Hammond, Chiara Tognaccini, Joanna Latasiewicz, Lisa Willemsen, Karsten Zengler, Menno Pj de Winther, Hal M Hoffman, Martin Philpott, Adam P Cribbs, Udo Oppermann, Nathan E Lewis, Joseph L Witztum, Ruth Yu, Annette R Atkins, Michael Downes, Ron M Evans, Christopher K Glass, Lars Bode, Philip Lsm Gordts
{"title":"人乳寡糖 3'sialyllactose 可减少小鼠低度炎症和动脉粥样硬化的发生。","authors":"Ariane R Pessentheiner, Nathanael J Spann, Chloe A Autran, Tae Gyu Oh, Kaare V Grunddal, Joanna Kc Coker, Chelsea D Painter, Bastian Ramms, Austin Wt Chiang, Chen-Yi Wang, Jason Hsiao, Yiwen Wang, Anthony Quach, Laela M Booshehri, Alexandra Hammond, Chiara Tognaccini, Joanna Latasiewicz, Lisa Willemsen, Karsten Zengler, Menno Pj de Winther, Hal M Hoffman, Martin Philpott, Adam P Cribbs, Udo Oppermann, Nathan E Lewis, Joseph L Witztum, Ruth Yu, Annette R Atkins, Michael Downes, Ron M Evans, Christopher K Glass, Lars Bode, Philip Lsm Gordts","doi":"10.1172/jci.insight.181329","DOIUrl":null,"url":null,"abstract":"<p><p>Macrophages contribute to the induction and resolution of inflammation and play a central role in chronic low-grade inflammation in cardiovascular diseases caused by atherosclerosis. Human milk oligosaccharides (HMOs) are complex unconjugated glycans unique to human milk that benefit infant health and act as innate immune modulators. Here, we identify the HMO 3'sialyllactose (3'SL) as a natural inhibitor of TLR4-induced low-grade inflammation in macrophages and endothelium. Transcriptome analysis in macrophages revealed that 3'SL attenuates mRNA levels of a selected set of inflammatory genes and promotes the activity of liver X receptor (LXR) and sterol regulatory element binding protein-1 (SREBP1). These acute antiinflammatory effects of 3'SL were associated with reduced histone H3K27 acetylation at a subset of LPS-inducible enhancers distinguished by preferential enrichment for CCCTC-binding factor (CTCF), IFN regulatory factor 2 (IRF2), B cell lymphoma 6 (BCL6), and other transcription factor recognition motifs. In a murine atherosclerosis model, both s.c. and oral administration of 3'SL significantly reduced atherosclerosis development and the associated inflammation. This study provides evidence that 3'SL attenuates inflammation by a transcriptional mechanism to reduce atherosclerosis development in the context of cardiovascular disease.</p>","PeriodicalId":14722,"journal":{"name":"JCI insight","volume":null,"pages":null},"PeriodicalIF":6.3000,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"The human milk oligosaccharide 3'sialyllactose reduces low-grade inflammation and atherosclerosis development in mice.\",\"authors\":\"Ariane R Pessentheiner, Nathanael J Spann, Chloe A Autran, Tae Gyu Oh, Kaare V Grunddal, Joanna Kc Coker, Chelsea D Painter, Bastian Ramms, Austin Wt Chiang, Chen-Yi Wang, Jason Hsiao, Yiwen Wang, Anthony Quach, Laela M Booshehri, Alexandra Hammond, Chiara Tognaccini, Joanna Latasiewicz, Lisa Willemsen, Karsten Zengler, Menno Pj de Winther, Hal M Hoffman, Martin Philpott, Adam P Cribbs, Udo Oppermann, Nathan E Lewis, Joseph L Witztum, Ruth Yu, Annette R Atkins, Michael Downes, Ron M Evans, Christopher K Glass, Lars Bode, Philip Lsm Gordts\",\"doi\":\"10.1172/jci.insight.181329\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Macrophages contribute to the induction and resolution of inflammation and play a central role in chronic low-grade inflammation in cardiovascular diseases caused by atherosclerosis. Human milk oligosaccharides (HMOs) are complex unconjugated glycans unique to human milk that benefit infant health and act as innate immune modulators. Here, we identify the HMO 3'sialyllactose (3'SL) as a natural inhibitor of TLR4-induced low-grade inflammation in macrophages and endothelium. Transcriptome analysis in macrophages revealed that 3'SL attenuates mRNA levels of a selected set of inflammatory genes and promotes the activity of liver X receptor (LXR) and sterol regulatory element binding protein-1 (SREBP1). These acute antiinflammatory effects of 3'SL were associated with reduced histone H3K27 acetylation at a subset of LPS-inducible enhancers distinguished by preferential enrichment for CCCTC-binding factor (CTCF), IFN regulatory factor 2 (IRF2), B cell lymphoma 6 (BCL6), and other transcription factor recognition motifs. In a murine atherosclerosis model, both s.c. and oral administration of 3'SL significantly reduced atherosclerosis development and the associated inflammation. This study provides evidence that 3'SL attenuates inflammation by a transcriptional mechanism to reduce atherosclerosis development in the context of cardiovascular disease.</p>\",\"PeriodicalId\":14722,\"journal\":{\"name\":\"JCI insight\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":6.3000,\"publicationDate\":\"2024-11-08\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"JCI insight\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1172/jci.insight.181329\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"JCI insight","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1172/jci.insight.181329","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
引用次数: 0

摘要

巨噬细胞有助于炎症的诱导和消退,并在动脉粥样硬化引起的心血管疾病的慢性低度炎症中发挥核心作用。人乳低聚糖(HMO)是人乳中特有的复杂非结合糖,有益于婴儿健康并可作为先天性免疫调节剂。在这里,我们发现 HMO 3'sialyllactose (3'SL) 是巨噬细胞和内皮细胞中 Toll-Like Receptor (TLR) 4 诱导的低度炎症的天然抑制剂。巨噬细胞的转录组分析表明,3'SL 可降低一组选定的炎症基因的 mRNA 水平,并促进肝 X 受体(LXR)和甾醇调节元件结合蛋白-1(SREBP)的活性。3'SL的这些急性抗炎作用与脂多糖(LPS)诱导的增强子子集组蛋白H3K27乙酰化减少有关,这些增强子优先富集了CCCTC结合因子(CTCF)、干扰素调节因子2(IRF2)、B细胞淋巴瘤6(BCL6)和其他转录因子识别基团。在小鼠动脉粥样硬化模型中,皮下注射和口服 3'SL 均能显著减少动脉粥样硬化的发展和相关炎症。这项研究提供的证据表明,3'SL 通过转录机制减轻炎症,从而减少心血管疾病中动脉粥样硬化的发展。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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
The human milk oligosaccharide 3'sialyllactose reduces low-grade inflammation and atherosclerosis development in mice.

Macrophages contribute to the induction and resolution of inflammation and play a central role in chronic low-grade inflammation in cardiovascular diseases caused by atherosclerosis. Human milk oligosaccharides (HMOs) are complex unconjugated glycans unique to human milk that benefit infant health and act as innate immune modulators. Here, we identify the HMO 3'sialyllactose (3'SL) as a natural inhibitor of TLR4-induced low-grade inflammation in macrophages and endothelium. Transcriptome analysis in macrophages revealed that 3'SL attenuates mRNA levels of a selected set of inflammatory genes and promotes the activity of liver X receptor (LXR) and sterol regulatory element binding protein-1 (SREBP1). These acute antiinflammatory effects of 3'SL were associated with reduced histone H3K27 acetylation at a subset of LPS-inducible enhancers distinguished by preferential enrichment for CCCTC-binding factor (CTCF), IFN regulatory factor 2 (IRF2), B cell lymphoma 6 (BCL6), and other transcription factor recognition motifs. In a murine atherosclerosis model, both s.c. and oral administration of 3'SL significantly reduced atherosclerosis development and the associated inflammation. This study provides evidence that 3'SL attenuates inflammation by a transcriptional mechanism to reduce atherosclerosis development in the context of cardiovascular disease.

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
JCI insight
JCI insight Medicine-General Medicine
CiteScore
13.70
自引率
1.20%
发文量
543
审稿时长
6 weeks
期刊介绍: JCI Insight is a Gold Open Access journal with a 2022 Impact Factor of 8.0. It publishes high-quality studies in various biomedical specialties, such as autoimmunity, gastroenterology, immunology, metabolism, nephrology, neuroscience, oncology, pulmonology, and vascular biology. The journal focuses on clinically relevant basic and translational research that contributes to the understanding of disease biology and treatment. JCI Insight is self-published by the American Society for Clinical Investigation (ASCI), a nonprofit honor organization of physician-scientists founded in 1908, and it helps fulfill the ASCI's mission to advance medical science through the publication of clinically relevant research reports.
期刊最新文献
A therapeutic HBV vaccine containing a checkpoint modifier enhances CD8+ T cell and antiviral responses. Pivotal roles for cancer cell-intrinsic mPGES-1 and autocrine EP4 signaling in suppressing antitumor immunity. SLC4A11 mediates ammonia import and promotes cancer stemness in hepatocellular carcinoma. Targeting heterogeneous tumor microenvironments in pancreatic cancer mouse models of metastasis by TGF-β depletion. Deletion of Gba in neurons, but not microglia, causes neurodegeneration in a Gaucher mouse model.
×
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