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首页> 外文期刊>The European Journal of Neuroscience >Rat microglial cells secrete predominantly the precursor of interleukin-1beta in response to lipopolysaccharide.
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Rat microglial cells secrete predominantly the precursor of interleukin-1beta in response to lipopolysaccharide.

机译:大鼠小胶质细胞主要分泌白介素-1β的前体,以响应脂多糖。

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摘要

Little is known on the forms of interleukin-1beta (IL-1beta) that are produced by microglial cells in the nervous system. Mixed glial cell cultures of rats produced IL-1beta in response to lipopolysaccharide (LPS). Using Western blot, pro-IL-1beta was found to be localized both intracellularly and in the supernatant, whereas mature IL-1beta was found only in the supernatant but in lower quantities than pro-IL-1beta. Immunocytochemistry confirmed that microglial cells are the exclusive source of IL-1beta. Blockade of the IL-1beta-converting enzyme (ICE) by Tyr-Val-Ala-Asp-aldehyde (YVAD-CHO) decreased the levels of mature IL-1beta but had no effect on pro-IL-1beta. Release of pro-IL-1beta was not associated with cell death nor with the extracellular release of ICE. Using gelatin zymography, glial cells were found to express constitutive matrix metalloproteinases (MMP) in the form of MMP-2. Exposure to LPS induced MMP-9 expression in a time-dependent manner similar to the pro-IL-1beta expression profile. MMP activation and inhibition experiments indicated a possible role of MMPs in the cleavage of pro-IL-1beta but not in the generation of mature IL-1beta. Microglial cells share with macrophages the ability to release large amounts of pro-IL-1beta of which the extracellular role remains to be determined.
机译:关于神经系统中小胶质细胞产生的白介素-1β(IL-1beta)的形式知之甚少。大鼠的混合神经胶质细胞培养物对脂多糖(LPS)产生IL-1β。使用蛋白质印迹,发现pro-IL-1beta位于细胞内和上清液中,而成熟的IL-1beta仅在上清液中发现,但含量低于pro-IL-1beta。免疫细胞化学证实,小胶质细胞是IL-1β的唯一来源。 Tyr-Val-Ala-Asp-醛(YVAD-CHO)对IL-1beta转化酶(ICE)的阻滞降低了成熟IL-1beta的水平,但对pro-IL-1beta没有影响。 IL-1β的释放与细胞死亡或ICE的细胞外释放均无关。使用明胶酶谱分析,发现神经胶质细胞以MMP-2的形式表达组成型基质金属蛋白酶(MMP)。暴露于LPS会以时间依赖性方式诱导MMP-9表达,类似于pro-IL-1beta表达谱。 MMP激活和抑制实验表明MMP可能在前IL-1beta的裂解中起作用,但在成熟IL-1beta的产生中不起作用。小胶质细胞与巨噬细胞共享释放大量前IL-1β的能力,其细胞外作用尚待确定。

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