首页> 外文期刊>Cell biology international. >IRGM promotes glioma M2 macrophage polarization through p62/TRAF6/NF-kappa B pathway mediated IL-8 production
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IRGM promotes glioma M2 macrophage polarization through p62/TRAF6/NF-kappa B pathway mediated IL-8 production

机译:IRGM通过P62 / TRAF6 / NF-Kappa B介导的IL-8生产促进胶质瘤M2巨噬细胞极化

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摘要

Alternatively activated (M2) macrophage promotes glioma progression and immune escape as the most immunocyte in glioma microenvironment. Finding out the key protein regulating M2 macrophage polarization is necessary for improving treatment. Whether immunity related GTPase M (IRGM) is involved in glioma development and M2 macrophage polarization is unknown. IRGM and M2 macrophage marker CD206 expression were examined using immunohistochemistry among 35 glioma and 11 non-cancerous brain specimens. We found IRGM scores were positively correlated with CD206 scores in glioma specimens and monocyte proportion in blood samples. A172 glioma cells transfected with either IRGM knock-down lentivirus (Lenti-IRGM) or control lentivirus (Lenti-HK) were subcutaneously injected into nude mice. In vivo, xenografted glioma size of the Lenti-IRGM group was smaller and had weaker fluorescence signal than Lenti-HK control group. Immunofluorescence results showed that there was obviously decreased IRGM, CD206, and IL-8 expression in the mice glioma of Lenti-IRGM group than Lenti-HK control group. In vitro, flow cytometry results showed that M2 polarization from THP-1 cocultured with Lenti-IRGM glioma cells decreased in contrast to that with Lenti-HK glioma cells; there were less interleukin-8 (IL-8) and macrophage inflammation protein 3-alpha (MIP-3 alpha), but more interleukin-6 (IL-6) in the supernatant of Lenti-IRGM glioma cells than matched control. Western blot and immunofluorescence displayed that IRGM strongly promoted sequestosome-1 (p62/SQSTM1), necrosis factor receptor-activating factor 6 (TRAF6) expression and NF-kappa B transportation to the nucleus. Realtime PCR results demonstrated IRGM also promoted NF-kappa B downstream cytokines IL-8 and MIP-3 alpha mRNA expression. These data suggested that IRGM could promote glioma development and M2 macrophage polarization by regulating p62/TRAF6/NF-kappa B pathway-mediated IL-8 production.
机译:可选地,活化(M2)巨噬细胞促进胶质瘤进展和免疫逸出作为胶质瘤微环境中最具免疫细胞。找出改善治疗所必需的键调节M2巨噬细胞极化的关键蛋白质。免疫相关GTPASE M(IRGM)是否参与胶质瘤发育,M2巨噬细胞极化未知。在35只胶质瘤和11种非癌性脑标本中使用免疫组织化学检查IRGM和M2巨噬细胞标记物CD206表达。我们发现IRGM评分与胶质瘤样品中的CD206分数与血液样品中的单核细胞比例呈正相关。将用IRGM倒下的慢病毒(LENTI-IRGM)或对照慢病毒(LENTI-HK)转染的A172胶质瘤细胞被皮下注射到裸鼠中。在体内,Lenti-Irgm组的异种胶质瘤大小较小,荧光信号比Lenti-HK对照组更弱。免疫荧光结果表明,在Lenti-IRGM组小鼠胶质瘤中显然降低了IRGM,CD206和IL-8表达,而不是Lenti-HK对照组。体外,流式细胞术的结果表明,与含有LENTI-HK胶质瘤细胞相比,与熊氏胶质瘤细胞的THP-1共有的M2偏振减少;白细胞介素-8(IL-8)和巨噬细胞炎症蛋白3-α(MIP-3α),但在比赛的上清液中的白细胞介素-6(IL-6)比匹配的对照。 Western印迹和免疫荧光显示IRGM强烈促进的封装-1(P62 / SQSTM1),坏死因子受体激活因子6(TRAF6)表达和NF-Kappa B对核的运输。实时PCR结果证明IRGM还促进了NF-Kappa下游细胞因子IL-8和MIP-3αmRNA表达。这些数据表明IRGM可以通过调节P62 / TRAF6 / NF-Kappa介导的IL-8生产来促进胶质瘤发展和M2巨噬细胞极化。

著录项

  • 来源
    《Cell biology international.》 |2019年第2期|共11页
  • 作者单位

    Guangzhou Med Univ Grad Sch Shenzhen Peoples Hosp 2 Brain Ctr Shenzhen Key Lab Neurosurg;

    Guangzhou Med Univ Grad Sch Shenzhen Peoples Hosp 2 Brain Ctr Shenzhen Key Lab Neurosurg;

    Guangzhou Med Univ Grad Sch Shenzhen Peoples Hosp 2 Brain Ctr Shenzhen Key Lab Neurosurg;

    Guangzhou Med Univ Grad Sch Shenzhen Peoples Hosp 2 Brain Ctr Shenzhen Key Lab Neurosurg;

    Sun Yat Sen Univ Canc Ctr Dept Neurosurg Neurooncol Guangzhou Guangdong Peoples R China;

    Guangzhou Med Univ Grad Sch Shenzhen Peoples Hosp 2 Brain Ctr Shenzhen Key Lab Neurosurg;

    Guangzhou Med Univ Grad Sch Shenzhen Peoples Hosp 2 Brain Ctr Shenzhen Key Lab Neurosurg;

    Guangzhou Med Univ Grad Sch Shenzhen Peoples Hosp 2 Brain Ctr Shenzhen Key Lab Neurosurg;

    Guangzhou Med Univ Grad Sch Shenzhen Peoples Hosp 2 Brain Ctr Shenzhen Key Lab Neurosurg;

    Guangzhou Med Univ Grad Sch Shenzhen Peoples Hosp 2 Brain Ctr Shenzhen Key Lab Neurosurg;

    Guangzhou Med Univ Grad Sch Shenzhen Peoples Hosp 2 Brain Ctr Shenzhen Key Lab Neurosurg;

    Guangzhou Med Univ Grad Sch Shenzhen Peoples Hosp 2 Brain Ctr Shenzhen Key Lab Neurosurg;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 细胞生物学;
  • 关键词

    glioma; immunity related GTPase M; interleukin-6; interleukin-8; macrophage inflammation protein 3-alpha; M2 macrophage;

    机译:胶质瘤;免疫相关GTP酶m;白细胞介素-6;白细胞介素-8;巨噬细胞炎症蛋白3-α;M2巨噬细胞;

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