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首页> 外文期刊>The European Journal of Neuroscience >Expression and regulation of interleukin-10 and interleukin-10 receptor in rat astroglial and microglial cells.
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Expression and regulation of interleukin-10 and interleukin-10 receptor in rat astroglial and microglial cells.

机译：白细胞介素10和白细胞介素10受体在大鼠星形胶质细胞和小胶质细胞中的表达和调控。

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Activated glial cells crucially contribute to brain inflammatory responses. Interleukin-10 (IL-10) is an important modulator of glial cell responses in the brain. In the present study we describe the expression of IL-10 and the IL-10 receptor (IL-10R1) in primary cocultures of rat microglial and astroglial cells. Using quantitative RT-PCR and ELISA, we show that IL-10 mRNA expression and subsequent IL-10 secretion is time-dependently induced by lipopolysaccharide (LPS). IL-10R1, however, is constitutively expressed in glial cell cocultures, as shown by RT-PCR and immunocytochemistry. Radioligand binding studies using 125I-IL-10 reveal that rat glial cells express a single binding site with an apparent affinity of approximately 600 pm for human IL-10. Observations in enriched cultures of either microglial or astroglial cells indicate that both cell types express IL-10 mRNA and are capable of secreting IL-10. Both cell types also express IL-10R1 mRNA and protein. However, in glial cell cocultures immunoreactive IL-10R1 protein is predominantly observed in astrocytes, suggesting that microglial expression of IL-10R1 in cocultures is suppressed by astrocytes. In addition, exogenous IL-10 is highly potent in down-regulating LPS-induced IL-1beta and IL-10 mRNA, and, at a higher dose, IL-10R1 mRNA in untreated and LPS-treated cultures, suggesting that IL-10 autoregulates its expression and inhibits that of IL-1beta at the transcriptional level. Together the findings support the concept that IL-10, produced by activated microglial and astroglial cells, modulates glia-mediated inflammatory responses through high-affinity IL-10 receptors via paracrine and autocrine interactions.
机译：活化的神经胶质细胞对脑部炎症反应至关重要。白介素10（IL-10）是大脑中神经胶质细胞反应的重要调节剂。在本研究中，我们描述了大鼠小胶质细胞和星形胶质细胞的原代培养中IL-10和IL-10受体（IL-10R1）的表达。使用定量RT-PCR和ELISA，我们显示IL-10 mRNA表达和随后的IL-10分泌是时间依赖性地被脂多糖（LPS）诱导的。然而，如RT-PCR和免疫细胞化学所示，IL-10R1在胶质细胞共培养物中组成性表达。使用125I-IL-10进行的放射性配体结合研究表明，大鼠神经胶质细胞表达单个结合位点，对人IL-10的表观亲和力约为600 pm。在小胶质细胞或星形胶质细胞的富集培养物中的观察结果表明，两种细胞类型均表达IL-10 mRNA，并且能够分泌IL-10。两种细胞类型还表达IL-10R1 mRNA和蛋白质。然而，在神经胶质细胞共培养物中，主要在星形胶质细胞中观察到免疫反应性IL-10R1蛋白，这表明星形胶质细胞抑制了IL-10R1在共培养物中的小胶质细胞表达。此外，外源性IL-10在下调LPS诱导的IL-1beta和IL-10 mRNA方面非常有效，而在较高剂量下，未经处理和LPS处理的培养物中IL-10R1 mRNA的表达较高，这表明IL-10自动调节其表达并在转录水平上抑制IL-1beta的表达。这些发现共同支持了由激活的小胶质细胞和星形胶质细胞产生的IL-10通过旁分泌和自分泌相互作用通过高亲和力IL-10受体调节胶质细胞介导的炎症反应的概念。

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