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首页> 外文期刊>Life sciences >Exosomal miR-21 secreted by IL-1 beta-primed-mesenchymal stem cells induces macrophage M2 polarization and ameliorates sepsis
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Exosomal miR-21 secreted by IL-1 beta-primed-mesenchymal stem cells induces macrophage M2 polarization and ameliorates sepsis

机译：由IL-1β-灌注 - 间充质干细胞分泌的外泌体miR-21诱导巨噬细胞M2偏振和改善败血症

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摘要

Sepsis occurs due to a damaging host response to infection and is the chief cause of death in most intensive care units. Mesenchymal stem cells (MSCs) exhibit immunomodulatory properties and can modulate key cells of the innate and adaptive immune systems through various effector mechanisms, such as exosomes. Exosomes and their microRNA (miRNA or miR) cargo including miR-21 can initiate profound phenotypic changes in the tumor microenvironment due to their intercellular communication transmitting the pleiotropic messages between different cell types, tissues, and body fluids. Here, we aimed to characterize the effect of miR-21 delivered from MSC-derived exosomes on the polarization of macrophages in a mouse sepsis model. First, we isolated exosomes from interleukin-1 beta (IL-1 beta)-pretreated murine MSCs (beta MSCs) and injected them into cecal ligation and puncture (CLP) septic models. We found that beta MSCs-derived exosomes could more effectively induce M2-like polarization of macrophages in vitro and in vivo. Administration of beta MSCs-derived exosomes attenuated the symptoms in septic mice more effectively and increased their survival rate as compared to exosomes released by naive MSCs. Importantly, we found that miR-21 was abundantly upregulated in MSCs upon IL-1 beta stimulation and packaged into exosomes. This exosomal miR-21 was transferred to macrophages, leading to M2 polarization in vitro and in vivo. The therapeutic efficacy of beta MSC-derived exosomes was partially lost upon miR-21 inhibition by its specific inhibitors. More specifically, we demonstrated beta MSCs-derived exosomes inhibited the effects of PDCD4, the target gene of miR-21, on macrophage polarization and sepsis. In conclusion, exosomal miR-21 emerged as a key mediator of IL-1 beta pretreatment induced immunomodulatory properties of MSCs. The study indicated a novel basis for therapeutic application of MSCs in sepsis.
机译：败血症是由于宿主对感染的破坏性反应而发生的，是大多数重症监护病房的主要死亡原因。间充质干细胞（Mesenchymal stem cells，MSCs）具有免疫调节特性，可以通过各种效应器机制（如外显体）调节先天性和适应性免疫系统的关键细胞。外泌体及其microRNA（miRNA或miR）载体，包括miR-21，由于其细胞间通讯，在不同细胞类型、组织和体液之间传递多效性信息，可引发肿瘤微环境的深刻表型变化。在这里，我们的目的是在小鼠脓毒症模型中描述从MSC衍生的外显体递送的miR-21对巨噬细胞极化的影响。首先，我们从白细胞介素-1β（IL-1β）预处理的小鼠骨髓间充质干细胞（β-MSCs）中分离出外质体，并将其注射到盲肠结扎和穿刺（CLP）脓毒症模型中。我们发现，在体外和体内，β-MSCs衍生的外质体可以更有效地诱导巨噬细胞的M2样极化。与未经处理的MSCs释放的外显体相比，给予β-MSCs衍生的外显体更有效地减轻脓毒症小鼠的症状，并提高其存活率。重要的是，我们发现在IL-1β刺激下，骨髓间充质干细胞中的miR-21大量上调，并打包成外显体。这种外体miR-21被转移到巨噬细胞，导致体外和体内的M2极化。在miR-21被其特异性抑制剂抑制后，β-MSC衍生的外显体的治疗效果部分丧失。更具体地说，我们证明了β-MSCs衍生的外显体抑制了miR-21靶基因PDCD4对巨噬细胞极化和脓毒症的影响。总之，外体miR-21是IL-1β预处理诱导的骨髓间充质干细胞免疫调节特性的关键介质。这项研究为骨髓间充质干细胞在脓毒症治疗中的应用提供了新的基础。

著录项

  • 来源
    《Life sciences》 |2021年第1期|共13页
  • 作者

    Yao Mengying; Cui Bing; Zhang Weihong; Ma Wentao; Zhao Gaofeng; Xing Lihua;

  • 作者单位

    Zhengzhou Univ Dept Resp Intens Care Unit Affiliated Hosp 1 1 Eastern Jianshe Rd Zhengzhou;

    Henan Univ Chinese Med Dept Nephrol Affiliated Hosp 1 Zhengzhou 450052 Peoples R China;

    Zhengzhou Univ Dept Anat Nursing Coll Zhengzhou 450052 Peoples R China;

    Zhengzhou Univ Dept Resp Intens Care Unit Affiliated Hosp 1 1 Eastern Jianshe Rd Zhengzhou;

    Zhengzhou Univ Dept Thorac Surg Affiliated Hosp 1 1 Eastern Jianshe Rd Zhengzhou 450052 Henan;

    Zhengzhou Univ Dept Resp Intens Care Unit Affiliated Hosp 1 1 Eastern Jianshe Rd Zhengzhou;

  • 收录信息
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 医药、卫生;
  • 关键词

    miR-21; Mesenchymal stem cells; Exosomes; Sepsis; PDCD4; IL-1 beta; Macrophages;

    机译：miR-21;间充质干细胞;外质体;败血症;PDCD4;IL-1β;巨噬细胞;

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