Ethanol inhibits cytokine-induced iNOS and sPLA2 in immortalized astrocytes: evidence for posttranscriptional site of ethanol action.

Ethanol inhibits cytokine-induced iNOS and sPLA2 in immortalized astrocytes: evidence for posttranscriptional site of ethanol action.
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乙醇抑制永生化星形胶质细胞中细胞因子诱导的 iNOS 和 sPLA2:乙醇作用转录后位点的证据。

DOI:
10.1007/bf02255981
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发表时间:
2001
影响因子:
11
通讯作者:
Sun,GY
Sun,GY
中科院分区:
医学1区
文献类型:
--
作者:
Wang,JH;Sun,GY

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慢性和过量的乙醇消耗已知会改变中枢神经系统(CNS)中的神经元和神经胶质细胞功能。星形胶质细胞是大脑中的主要细胞类型。这些免疫活性细胞能够响应促炎细胞因子和内毒素,其刺激导致基因诱导的转录途径,包括诱导型一氧化氮合酶(iNOS)和分泌型磷脂酶A2(sPLA 2)。本研究探讨了乙醇对永生化星形胶质细胞(immortalized astrocytes,DITNC)诱导的iNOS和sPLA 2的影响。当DITNC细胞暴露于乙醇(0-200 mM)为4小时,随后刺激细胞因子为16小时,NO的产生减少,乙醇浓度从50 mM开始增加。在乙醇浓度高于100 mM,乙醇也抑制了精氨酸诱导的sPLA 2释放到培养基中。乙醇对NO产生的抑制作用与iNOS蛋白和NOS酶活性的降低相一致,而与iNOS和sPLA_2mRNA以及NF-κ B与DNA的结合无关。乙醇对奎宁诱导的NO产生的抑制作用也依赖于乙醇暴露于细胞的时间,但加入高达200 μM的乙醛并没有引起任何变化。两者合计,这些结果提供了证据的转录后模式的乙醇作用于星形胶质细胞中的NO产生的细胞因子诱导途径。
Chronic and excessive ethanol consumption is known to alter neuron and glial cell functions in the central nervous system (CNS). Astrocytes comprise the major cell type in the brain. These immune active cells are capable of responding to proinflammatory cytokines and endotoxins, which stimulate transcriptional pathways leading to induction of genes, including the inducible nitric oxide synthase (iNOS) and secretory phospholipase A2(sPLA2). In this study, we investigate the effects of ethanol on cytokine-induced iNOS and sPLA2in immortalized astrocytes (DITNC). When DITNC cells were exposed to ethanol (0–200 mM) for 4 h prior to subsequent stimulation with cytokines for 16 h, NO production decreased with increasing ethanol concentrations starting from 50 mM. At ethanol concentrations higher than 100 mM, ethanol also inhibited cytokine-induced sPLA2release into the culture medium. The inhibitory effect of ethanol on NO production corresponds well with the decrease in iNOS protein and NOS enzyme activity, but not with iNOS and sPLA2mRNA nor binding of NF-ĸB to DNA. The inhibition of cytokine-induced NO production by ethanol was also dependent on the time of ethanol exposure to the cells, but addition of acetaldehyde up to 200 µM did not elicit any changes. Taken together, these results provide evidence for a posttranscriptional mode of ethanol action on the cytokine induction pathway for NO production in astrocytes.
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