Strawberry notch homolog 2 is a novel inflammatory response factor predominantly but not exclusively expressed by astrocytes in the central nervous system.
Strawberry notch homolog 2 is a novel inflammatory response factor predominantly but not exclusively expressed by astrocytes in the central nervous system.
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作者：
Grill M;Syme TE;Noçon AL;Lu AZ;Hancock D;Rose-John S;Campbell IL
白介素6(IL-6)参与宿主对中枢神经系统(CNS)损伤和感染的反应。我们在小鼠星形胶质细胞中发现草莓缺口同源物2(Sbno2)是一个受IL-6刺激的基因。Sbno2是果蝇中sno基因的小鼠同源基因，但人们对这种哺乳动物基因的调节或功能知之甚少。在这里，我们研究了Sbno2基因在体外星形胶质细胞和全身内毒素注射后在小鼠中枢神经系统中的调节。在培养的鼠和人星形胶质细胞中，高IL-6(IL-6 + 可溶性IL-6受体)显著上调Sbno2基因的表达，且呈剂量和时间依赖关系。其他糖蛋白130细胞因子家族成员以及促炎细胞因子IL-1β和肿瘤坏死因子α也显著上调了小鼠星形胶质细胞中Sbno2的表达水平。这些变化反映在SBNO2蛋白水平的相应变化上。抑制蛋白质合成导致Sbno2基因表达增加，但不能阻断高IL-6诱导的Sbno2基因表达上调。转录抑制导致高IL-6诱导的星形胶质细胞Sbno2基因表达迅速下降，提示Sbno2基因的表达很不稳定。小鼠腹腔注射脂多糖后，脑组织中Sbno2基因表达水平显著升高。细胞定位研究表明，Sbno2mRNA的这种增加主要发生在星形胶质细胞和脉络丛中，以及一些小胶质细胞、内皮细胞和神经元中。这些发现与SBNO2在星形胶质细胞和中枢神经系统其他细胞中作为急性炎症反应基因发挥作用是一致的。Glia 2015；63：1738-1752
Interleukin‐6 (IL‐6) participates in the host response to injury and infection in the central nervous system (CNS). We identified strawberry notch homolog 2 (Sbno2) as an IL‐6‐stimulated gene in murine astrocytes. Sbno2 is a mouse homolog of the sno gene in Drosophila but little is known about the regulation or function of the mammalian gene. Here we examined the regulation of the Sbno2 gene in astrocytes in vitro and in the murine CNS following systemic endotoxin administration. In murine and human cultured astrocytes, Sbno2 gene expression was significantly upregulated in a dose‐ and time‐dependent fashion by hyper‐IL‐6 (IL‐6 + soluble IL‐6 receptor). The level of Sbno2 mRNA was also upregulated significantly in murine astrocytes by other glycoprotein130 cytokine‐family members and the pro‐inflammatory cytokines interleukin‐1 beta and tumor necrosis factor alpha. These changes were reflected by corresponding alterations in the level of the SBNO2 protein. Inhibiting protein synthesis resulted in higher Sbno2 mRNA and did not abolish the upregulation of Sbno2 mRNA mediated by hyper‐IL‐6. Inhibition of transcription led to a rapid reduction in hyper‐IL‐6‐induced Sbno2 mRNA in astrocytes suggesting that the Sbno2 mRNA is quite unstable. Following intra‐peritoneal lipopolysaccharide injection in mice, Sbno2 mRNA levels in the brain were significantly increased. Cellular localization studies revealed that this increase in Sbno2 mRNA occurred predominantly in astrocytes and in the choroid plexus and in some microglia, endothelial cells, and neurons. These findings are consistent with SBNO2 functioning as an acute inflammatory response gene in astrocytes as well as other cells in the CNS. GLIA 2015;63:1738–1752