Inhibition of inducible nitric oxide synthase and interleukin-1β expression by tunicamycin in cultured glial cells exposed to lipopolysaccharide
Inhibition of inducible nitric oxide synthase and interleukin-1β expression by tunicamycin in cultured glial cells exposed to lipopolysaccharide
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DOI：
10.1016/j.brainres.2014.02.035
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发表时间：
2014-04-16
期刊：
影响因子：
2.9
通讯作者：
Ozawa, Koichiro
中科院分区：
文献类型：
--
作者：
Hosoi, Toru;Noguchi, Jun;Ozawa, Koichiro
内质网（ER）应激最近已被牵连在人类疾病，如阿尔茨海默病（AD）和帕金森病（PD）。然而，免疫系统，ER应激和神经退行性疾病的发展之间的联系尚未详细阐明。用脂多糖（LPS）和/或衣霉素（Tm）处理原代培养的小鼠星形胶质细胞，然后用RT-PCR、ELISA和Western blotting检测诱导型一氧化氮合酶（iNOS）和白细胞介素（IL）-1 β的水平。通过诱导iNOS和IL-1 β来测量，LPS激活免疫系统引发星形胶质细胞中的炎症反应。Tm诱导的ER应激在蛋白水平抑制LPS诱导的IL-1 β和iNOS的表达。另一方面，单独的ER应激不诱导IL-1 β或iNOS的表达。ER应激对iNOS和IL-1 β的抑制作用可能不是转录介导的，因为我们没有观察到mRNA水平的抑制。LPS诱导的iNOS蛋白水平在LPS不存在的情况下通过Tm后处理而减弱。总之，这些结果表明，ER应激负调控LPS激活的星形胶质细胞中IL-1 β和iNOS的表达。(C)2014爱思唯尔有限公司版权所有。
Endoplasmic reticulum (ER) stress has recently been implicated in human diseases such as Alzheimer's disease (AD) and Parkinson's disease (PD). However, the link between the immune system, ER stress, and the development of neurodegenerative diseases has not yet been clarified in detail. Mouse primary cultured astrocytes were treated with lipopolysaccharide (LPS) and/or tunicamycin (Tm), and inducible nitric oxide synthase (iNOS) and interleuldn (IL)-1 beta levels were then measured using RT-PCR, ELISA, and Western blotting. Activation of the immune system by LPS triggered inflammatory responses in astrocytes, as measured by the induction of iNOS and IL-1 beta. Tm-induced ER stress inhibited the LPS-induced expression of IL-1 beta and iNOS at the protein level. On the other hand, ER stress alone did not induce the expression of IL-1 beta or iNOS. The inhibitory effect of ER stress on iNOS and IL-1 beta may not be mediated transcriptionally as we did not observe inhibition at the mRNA level. LPS-induced iNOS protein levels were attenuated by the Tm post-treatment in the absence of LPS. Overall, these results suggest that ER stress negatively regulates the expression of IL-1 beta and iNOS in LPS-activated astrocytes. (C) 2014 Elsevier B.V. All rights reserved.