Glucagon-like peptide-1 inhibits LPS-induced IL-1β production in cultured rat astrocytes
Glucagon-like peptide-1 inhibits LPS-induced IL-1β production in cultured rat astrocytes
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DOI：
10.1016/j.neures.2006.04.008
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发表时间：
2006-08-01
影响因子：
2.9
通讯作者：
Oka, Jun-Ichiro
中科院分区：
文献类型：
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作者：
Iwai, Takashi;Ito, Satoshi;Oka, Jun-Ichiro
神经胶质在神经退行性疾病的神经毒性中起重要作用。在这项研究中，我们研究了胰高血糖素样肽-1（GLP-1）及其受体的表达，以及GLP-1对脂多糖（LPS）诱导的胶质细胞IL-1 β mRNA表达和IL-1 β产生的影响。在变形小胶质细胞中观察到GLP-1样免疫反应性，但在分支小胶质细胞或星形胶质细胞中未观察到。在星形胶质细胞和小胶质细胞中均观察到GLP-1结合和GLP-1受体mRNA表达。GLP-1诱导的小胶质细胞形态学变化从分枝型变为变形虫型，表明内源性GLP-1的产生和释放增加。GLP-1阻止LPS诱导的IL-1 β mRNA表达，而这种作用反过来又被腺苷酸环化酶抑制剂SQ 22536预处理抑制。GLP-1还增加星形胶质细胞中cAMP浓度和cAMP反应元件结合蛋白磷酸化。这些结果表明，GLP-1可能是中枢神经系统炎症的调节剂。(c)2006年Elsevier爱尔兰有限公司和日本神经科学学会。All rights reserved.
Glia play an important role in neurotoxicity in neurodegenerative diseases. In this study, we investigated the expression of glucagon-like peptide-1 (GLP-1) and its receptor, and the effects of GLP-1 on lipopolysaccharide (LPS)-induced IL-1 beta mRNA expression and IL-1 beta production in glia. GLP-1-like immunoreactivity was observed in amoeboid microglia, but not ramified microglia or astrocytes. GLP-1 binding and GLP-1 receptor mRNA expression were observed in both astrocytes and microglia. GLP-1-induced morphological changes in microglia from the ramified type to the amoeboid type, suggesting an increase in production and release of endogenous GLP-1. GLP-1 prevented the LPS-induced IL-I beta mRNA expression, which effect was, in turn, inhibited by pretreatment with SQ22536, an adenylate cyclase inhibitor. GLP-1 also increased cAMP concentration and cAMP response element-binding protein phosphorylation in astrocytes. These results suggest that GLP-1 may be a modulator of inflammation in the central nervous system. (c) 2006 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.