C-C Motif Chemokine 2 Regulates Macrophage Polarization and Contributes to Myocardial Infarction Healing.

IF 1.9 4区 医学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY Journal of Interferon and Cytokine Research Pub Date : 2024-02-01 Epub Date: 2023-12-28 DOI:10.1089/jir.2023.0132
Liangwei Chen, Dihao Pan, Yiran Zhang, Enfan Zhang, Liang Ma
{"title":"C-C Motif Chemokine 2 Regulates Macrophage Polarization and Contributes to Myocardial Infarction Healing.","authors":"Liangwei Chen, Dihao Pan, Yiran Zhang, Enfan Zhang, Liang Ma","doi":"10.1089/jir.2023.0132","DOIUrl":null,"url":null,"abstract":"<p><p>Macrophages are crucial immune cells that play essential roles in the healing of myocardial infarction (MI), undergoing continuous polarization throughout this process. C-C motif chemokine 2 (CCL2) is a chemokine that regulates inflammatory responses during MI. However, the extent to which CCL2 influences macrophage polarization and MI healing remains incompletely understood. In this study, we investigate the role of CCL2 in macrophage polarization and MI healing. Our findings reveal that CCL2 is differentially expressed in lipopolysaccharide (LPS)-induced M1 and interleukin (IL)-4-induced M2 RAW264.7 macrophages. Knockdown of CCL2 attenuates TNF-α secretion stimulated by LPS, while overexpression of CCL2 mitigates IL-10 production triggered by IL-4 in these macrophages. Moreover, CCL2 deficiency disrupts LPS-induced M1 polarization, whereas CCL2 overexpression reduces M2 polarization of RAW264.7 macrophages induced by IL-4. Further exploration indicates that the promotion of M1 polarization by CCL2 is significantly impaired by inhibition of the p38-mediated MAPK pathway and NF-κB pathway. In a MI mouse model, CCL2 knockdown remarkably reduces infarct size, collagen synthesis, and the expression of cardiac fibrosis and hypertrophy markers. The activity of the p38-mediated MAPK pathway and NF-κB pathway is downregulated by CCL2 knockdown as well. Additionally, the number of total macrophages and M1 macrophages in the infarct decreases, while the number of M2 macrophages increases upon CCL2 deficiency. In conclusion, these results suggest that CCL2 is a key regulator of macrophage polarization, controlling MI healing <i>in vivo</i>.</p>","PeriodicalId":16261,"journal":{"name":"Journal of Interferon and Cytokine Research","volume":null,"pages":null},"PeriodicalIF":1.9000,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Interferon and Cytokine Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1089/jir.2023.0132","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/12/28 0:00:00","PubModel":"Epub","JCR":"Q4","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Macrophages are crucial immune cells that play essential roles in the healing of myocardial infarction (MI), undergoing continuous polarization throughout this process. C-C motif chemokine 2 (CCL2) is a chemokine that regulates inflammatory responses during MI. However, the extent to which CCL2 influences macrophage polarization and MI healing remains incompletely understood. In this study, we investigate the role of CCL2 in macrophage polarization and MI healing. Our findings reveal that CCL2 is differentially expressed in lipopolysaccharide (LPS)-induced M1 and interleukin (IL)-4-induced M2 RAW264.7 macrophages. Knockdown of CCL2 attenuates TNF-α secretion stimulated by LPS, while overexpression of CCL2 mitigates IL-10 production triggered by IL-4 in these macrophages. Moreover, CCL2 deficiency disrupts LPS-induced M1 polarization, whereas CCL2 overexpression reduces M2 polarization of RAW264.7 macrophages induced by IL-4. Further exploration indicates that the promotion of M1 polarization by CCL2 is significantly impaired by inhibition of the p38-mediated MAPK pathway and NF-κB pathway. In a MI mouse model, CCL2 knockdown remarkably reduces infarct size, collagen synthesis, and the expression of cardiac fibrosis and hypertrophy markers. The activity of the p38-mediated MAPK pathway and NF-κB pathway is downregulated by CCL2 knockdown as well. Additionally, the number of total macrophages and M1 macrophages in the infarct decreases, while the number of M2 macrophages increases upon CCL2 deficiency. In conclusion, these results suggest that CCL2 is a key regulator of macrophage polarization, controlling MI healing in vivo.

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
C-C Motif趋化因子2调控巨噬细胞极化并促进心肌梗死愈合
巨噬细胞是重要的免疫细胞,在心肌梗塞(MI)愈合过程中发挥着至关重要的作用,并在整个过程中不断分化。C-C motif趋化因子2(CCL2)是一种趋化因子,可调节心肌梗死过程中的炎症反应。然而,CCL2 对巨噬细胞极化和心肌梗死愈合的影响程度仍不完全清楚。在本研究中,我们探讨了 CCL2 在巨噬细胞极化和 MI 愈合中的作用。我们的研究结果表明,CCL2在脂多糖(LPS)诱导的M1和白细胞介素(IL)-4诱导的M2 RAW264.7巨噬细胞中表达不同。敲除 CCL2 可减轻 LPS 刺激的 TNF-α 分泌,而过表达 CCL2 则可减轻 IL-4 在这些巨噬细胞中引发的 IL-10 的产生。此外,缺乏 CCL2 会破坏 LPS 诱导的 M1 极化,而过表达 CCL2 则会降低 IL-4 诱导的 RAW264.7 巨噬细胞的 M2 极化。进一步的研究表明,抑制 p38 介导的 MAPK 通路和 NF-κB 通路会显著削弱 CCL2 对 M1 极化的促进作用。在心肌梗死小鼠模型中,CCL2 的敲除可显著缩小梗死面积、减少胶原合成、降低心脏纤维化和肥大标志物的表达。CCL2 基因敲除还能降低 p38 介导的 MAPK 通路和 NF-κB 通路的活性。此外,CCL2 缺乏时,梗死区总巨噬细胞和 M1 巨噬细胞的数量减少,而 M2 巨噬细胞的数量增加。总之,这些结果表明,CCL2 是巨噬细胞极化的关键调节因子,控制着体内 MI 的愈合。
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
3.80
自引率
0.00%
发文量
78
审稿时长
2.2 months
期刊介绍: Journal of Interferon & Cytokine Research (JICR) provides the latest groundbreaking research on all aspects of IFNs and cytokines. The Journal delivers current findings on emerging topics in this niche community, including the role of IFNs in the therapy of diseases such as multiple sclerosis, the understanding of the third class of IFNs, and the identification and function of IFN-inducible genes.
期刊最新文献
Dual Time-Dependent Effects of Interleukin-33 Administration on the Kidney Postmyocardial Infarction. Integrated Analysis of Noncoding RNAs (PVT-1 and miR-200c) and Their Correlation with STAT4/IL-6 Axis as Reliable Biomarkers for COVID-19 Severity. IL-4 Downregulates PD-L1 Level Via SOCS1 Upregulation-Induced JNK Deactivation to Enhance Antitumor Immunity in In Vitro Colorectal Cancer. Multifarious Aspect of Cytokines as an Immuno-Therapeutic for Various Diseases. The Impact of Chemokine-Like Receptor 1 Gene Knockout on Lipopolysaccharide-Induced Epididymo-Orchitis in Mice.
×
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