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}
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.
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.