在脂多糖诱导的神经炎症中,白细胞介素-37通过MyD88/NF-κB通路调节小胶质细胞表型并抑制炎症反应。

IF 4.8 3区 医学 Q2 CELL BIOLOGY
Jingwen Zhang, Muhammad Abid Hayat, Yu Si, Tao Guo, Yinying Ni, Qian Wang, Yancheng Hong, Yudie Cao, Sijia He, Zijuan Weng, Fengmei Li, Hao Zuo, Xin Sun, Bo Chen, Jiabo Hu
{"title":"在脂多糖诱导的神经炎症中,白细胞介素-37通过MyD88/NF-κB通路调节小胶质细胞表型并抑制炎症反应。","authors":"Jingwen Zhang, Muhammad Abid Hayat, Yu Si, Tao Guo, Yinying Ni, Qian Wang, Yancheng Hong, Yudie Cao, Sijia He, Zijuan Weng, Fengmei Li, Hao Zuo, Xin Sun, Bo Chen, Jiabo Hu","doi":"10.1007/s00011-025-02048-x","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>Interleukin-37 (IL-37), an anti-inflammatory cytokine within the interleukin-1 (IL-1) family, exhibits immunomodulatory properties. Here we evaluate the effects of IL-37 on microglia in neuroinflammation and its potential mechanisms.</p><p><strong>Methods: </strong>C57BL/6 mice were injected intraperitoneally with 1 µg of recombinant human IL-37 protein (rhIL-37), and 24 h later with lipopolysaccharide (LPS) (5 mg/kg) to induce neuroinflammation. After 2-h pretreatment of BV2 cells with rhIL-37 (100 ng/mL), an in vitro model was established by treating with LPS (100 ng/mL). Mice were assessed for behavioral tests, and neuronal damage was evaluated by Nissl staining and hematoxylin and eosin staining. The expression of Iba1, CD86, CD206, and NF-κB were detected by immunofluorescence staining, and inflammatory mediators and pathway proteins were evaluated by ELISA, qRT-PCR, and Western blot.</p><p><strong>Results: </strong>IL-37 significantly ameliorated LPS-induced behavioral deficits and protected mice from inflammatory injury. In vitro experiments suggested that IL-37 modulates polarization of microglia from M1 to M2 phenotype, along with reducing pro-inflammatory cytokine production. Moreover, IL-37 attenuated the production of NF-κB and MyD88.</p><p><strong>Conclusions: </strong>IL-37 regulates microglia against neuroinflammatory responses by blocking the MyD88/NF-κB pathway and shows for the first time how IL-37 influences the phenotype of microglia, suggesting a potential therapeutic target for neuroinflammation.</p>","PeriodicalId":13550,"journal":{"name":"Inflammation Research","volume":"74 1","pages":"87"},"PeriodicalIF":4.8000,"publicationDate":"2025-05-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Interleukin-37 modulates microglial phenotype and inhibits inflammatory response via the MyD88/NF-κB pathway in lipopolysaccharide-induced neuroinflammation.\",\"authors\":\"Jingwen Zhang, Muhammad Abid Hayat, Yu Si, Tao Guo, Yinying Ni, Qian Wang, Yancheng Hong, Yudie Cao, Sijia He, Zijuan Weng, Fengmei Li, Hao Zuo, Xin Sun, Bo Chen, Jiabo Hu\",\"doi\":\"10.1007/s00011-025-02048-x\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>Interleukin-37 (IL-37), an anti-inflammatory cytokine within the interleukin-1 (IL-1) family, exhibits immunomodulatory properties. Here we evaluate the effects of IL-37 on microglia in neuroinflammation and its potential mechanisms.</p><p><strong>Methods: </strong>C57BL/6 mice were injected intraperitoneally with 1 µg of recombinant human IL-37 protein (rhIL-37), and 24 h later with lipopolysaccharide (LPS) (5 mg/kg) to induce neuroinflammation. After 2-h pretreatment of BV2 cells with rhIL-37 (100 ng/mL), an in vitro model was established by treating with LPS (100 ng/mL). Mice were assessed for behavioral tests, and neuronal damage was evaluated by Nissl staining and hematoxylin and eosin staining. The expression of Iba1, CD86, CD206, and NF-κB were detected by immunofluorescence staining, and inflammatory mediators and pathway proteins were evaluated by ELISA, qRT-PCR, and Western blot.</p><p><strong>Results: </strong>IL-37 significantly ameliorated LPS-induced behavioral deficits and protected mice from inflammatory injury. In vitro experiments suggested that IL-37 modulates polarization of microglia from M1 to M2 phenotype, along with reducing pro-inflammatory cytokine production. Moreover, IL-37 attenuated the production of NF-κB and MyD88.</p><p><strong>Conclusions: </strong>IL-37 regulates microglia against neuroinflammatory responses by blocking the MyD88/NF-κB pathway and shows for the first time how IL-37 influences the phenotype of microglia, suggesting a potential therapeutic target for neuroinflammation.</p>\",\"PeriodicalId\":13550,\"journal\":{\"name\":\"Inflammation Research\",\"volume\":\"74 1\",\"pages\":\"87\"},\"PeriodicalIF\":4.8000,\"publicationDate\":\"2025-05-29\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Inflammation Research\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s00011-025-02048-x\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Inflammation Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00011-025-02048-x","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

目的:白细胞介素-37 (IL-37)是白细胞介素-1 (IL-1)家族中的一种抗炎细胞因子,具有免疫调节特性。在此,我们评估了IL-37在神经炎症中对小胶质细胞的作用及其可能的机制。方法:C57BL/6小鼠腹腔注射重组人IL-37蛋白(rhIL-37) 1µg, 24 h后注射脂多糖(LPS) (5 mg/kg)诱导神经炎症。用rhIL-37 (100 ng/mL)预处理BV2细胞2 h后,用LPS (100 ng/mL)处理BV2细胞建立体外模型。采用尼氏染色、苏木精和伊红染色对小鼠进行行为学检查,观察神经元损伤情况。采用免疫荧光染色法检测Iba1、CD86、CD206和NF-κB的表达,采用ELISA、qRT-PCR和Western blot检测炎症介质和通路蛋白的表达。结果:IL-37可显著改善lps诱导的行为缺陷,保护小鼠免受炎症损伤。体外实验表明,IL-37调节小胶质细胞从M1表型到M2表型的极化,同时减少促炎细胞因子的产生。此外,IL-37可减弱NF-κB和MyD88的产生。结论:IL-37通过阻断MyD88/NF-κB通路调节小胶质细胞抗神经炎症反应,首次揭示了IL-37如何影响小胶质细胞的表型,提示了神经炎症的潜在治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Interleukin-37 modulates microglial phenotype and inhibits inflammatory response via the MyD88/NF-κB pathway in lipopolysaccharide-induced neuroinflammation.

Objective: Interleukin-37 (IL-37), an anti-inflammatory cytokine within the interleukin-1 (IL-1) family, exhibits immunomodulatory properties. Here we evaluate the effects of IL-37 on microglia in neuroinflammation and its potential mechanisms.

Methods: C57BL/6 mice were injected intraperitoneally with 1 µg of recombinant human IL-37 protein (rhIL-37), and 24 h later with lipopolysaccharide (LPS) (5 mg/kg) to induce neuroinflammation. After 2-h pretreatment of BV2 cells with rhIL-37 (100 ng/mL), an in vitro model was established by treating with LPS (100 ng/mL). Mice were assessed for behavioral tests, and neuronal damage was evaluated by Nissl staining and hematoxylin and eosin staining. The expression of Iba1, CD86, CD206, and NF-κB were detected by immunofluorescence staining, and inflammatory mediators and pathway proteins were evaluated by ELISA, qRT-PCR, and Western blot.

Results: IL-37 significantly ameliorated LPS-induced behavioral deficits and protected mice from inflammatory injury. In vitro experiments suggested that IL-37 modulates polarization of microglia from M1 to M2 phenotype, along with reducing pro-inflammatory cytokine production. Moreover, IL-37 attenuated the production of NF-κB and MyD88.

Conclusions: IL-37 regulates microglia against neuroinflammatory responses by blocking the MyD88/NF-κB pathway and shows for the first time how IL-37 influences the phenotype of microglia, suggesting a potential therapeutic target for neuroinflammation.

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
Inflammation Research
Inflammation Research 医学-免疫学
CiteScore
9.90
自引率
1.50%
发文量
134
审稿时长
3-8 weeks
期刊介绍: Inflammation Research (IR) publishes peer-reviewed papers on all aspects of inflammation and related fields including histopathology, immunological mechanisms, gene expression, mediators, experimental models, clinical investigations and the effect of drugs. Related fields are broadly defined and include for instance, allergy and asthma, shock, pain, joint damage, skin disease as well as clinical trials of relevant drugs.
×
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
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
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 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信