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Synthetic Prion Peptide 106-126 Resulted in an Increase Matrix Metalloproteinases and Inflammatory Cytokines from Rat Astrocytes and Microglial Cells

机译:合成Pri蛋白肽106-126导致大鼠星形胶质细胞和小胶质细胞的基质金属蛋白酶和炎性细胞因子增加

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摘要

It has been shown that the accumulation of prion in the cytoplasm can result in neurodegenerative disorders. Synthetic prion peptide 106-126 (PrP) is a glycoprotein that is expressed predominantly by neurons and other cells, including glial cells. Prion-induced chronic neurodegeneration has a substantial inflammatory component, and an increase in the levels of matrix metalloproteinases (MMPs) may play an important role in neurodegenerative development and progression. However, the expression of MMPs in PrP induced rat astrocytes and microglia has not yet been compared. Thus, in this study, we examined the fluorescence intensity of CD11b positive microglia and Glial Fibrillary Acidic Protein (GFAP) positive astrocytes and found that the fluorescent intensity was increased following incubation with PrP at 24 hours in a dose-dependent manner. We also observed an increase in interleukin-1 beta (IL-1β) and tumor necrosis factor alpha (TNF-α) protein expression, which are initial inflammatory cytokines, in both PrP induced astrocytes and microglia. Furthermore, an increase MMP-1, 3 and 11 expressions in PrP induced astrocytes and microglia was observed by real time PCR. Our results demonstrated PrP induced activation of astrocytes and microglia respectively, which resulted in an increase in inflammatory cytokines and MMPs expression. These results provide the insight into the different sensitivities of glial cells to PrP.
机译:已经显示of蛋白在细胞质中的积累可导致神经退行性疾病。合成pr病毒肽106-126(PrP)是一种糖蛋白,主要由神经元和其他细胞(包括神经胶质细胞)表达。 on病毒引起的慢性神经退行性变具有重要的炎症成分,基质金属蛋白酶(MMPs)水平的升高可能在神经退行性发展和进程中起重要作用。但是,尚未对PrP诱导的大鼠星形胶质细胞和小胶质细胞中MMPs的表达进行比较。因此,在这项研究中,我们检查了CD11b阳性小胶质细胞和胶质原纤维酸性蛋白(GFAP)阳性星形胶质细胞的荧光强度,发现与PrP孵育24小时后,荧光强度呈剂量依赖性增加。我们还观察到在PrP诱导的星形胶质细胞和小胶质细胞中,白细胞介素1β(IL-1β)和肿瘤坏死因子α(TNF-α)蛋白表达增加,它们是初始的炎症细胞因子。此外,通过实时PCR观察到PrP诱导的星形胶质细胞和小胶质细胞中MMP-1、3和11的表达增加。我们的结果证明PrP分别诱导星形胶质细胞和小胶质细胞的激活,从而导致炎症细胞因子和MMPs表达的增加。这些结果为了解神经胶质细胞对PrP的不同敏感性提供了见识。

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