α-melanocyte-stimulating hormone inhibits NF-κB activation and IκBα degradation in human glioma cells and in experimental brain inflammation
α-melanocyte-stimulating hormone inhibits NF-κB activation and IκBα degradation in human glioma cells and in experimental brain inflammation
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DOI：
10.1006/exnr.1999.7064
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发表时间：
1999-06-01
影响因子：
5.3
通讯作者：
Lipton, JM
中科院分区：
文献类型：
--
作者：
Ichiyama, T;Zhao, H;Lipton, JM
神经肽α-黑素细胞刺激激素（α-MSH）调节脑组织和外周炎性细胞中促炎细胞因子的产生。这些促炎细胞因子的基因转录受核因子κ B（NF-κ B）调节。NF-κ B也被促炎细胞因子激活。细胞质抑制剂I κ B α蛋白的降解导致NF-κ B的活化。由于越来越多的证据表明NF-κ B参与脑损伤、炎症和神经退行性疾病，我们检测了α-MSH是否抑制人胶质瘤细胞（A-172）和小鼠脑中脂多糖（LPS）诱导的NF-κ B的活化并限制I κ B α蛋白的降解。用LPS刺激的A-172细胞和整个小鼠脑的核提取物的电泳迁移率变化分析显示，α-MSH确实抑制NF-κ B活化。Western印迹分析表明，α-MSH在体外（胶质瘤细胞）和体内（脑组织）保留了I κ B α蛋白的表达。氯霉素乙酰转移酶实验表明，α-MSH抑制LPS诱导的A-172细胞NF-κ B依赖性报告基因的表达。该发现与α-MSH在CNS炎症中的抗炎作用通过肽诱导的I κ B α蛋白降解抑制调节NF-κ B活化而发生的可能性一致。(C)北京：科学出版社.
The neuropeptide alpha-melanocyte-stimulating hormone (alpha-MSH) modulates production of proinflammatory cytokines in brain tissue and in peripheral inflammatory cells. Transcription of the genes for these proinflammatory cytokines is regulated by the nuclear factor kappa B (NF-kappa B). NF-kappa B is also activated by proinflammatory cytokines. Degradation of the cytoplasmic inhibitor I kappa B alpha protein results in activation of NF-kappa B. Because of increasing evidence that NF-kappa B is involved in brain injury and inflammation and neurodegenerative disease, we examined whether alpha-MSH inhibits activation of NF-kappa B and limits degradation of I kappa B alpha protein induced by lipopolysaccharide (LPS) in human glioma cells (A-172) and in mouse brain. Electrophoretic mobility shift assays of nuclear extracts from A-172 cells and whole mouse brains stimulated with LPS revealed that alpha-MSH does suppress NF-kappa B activation. Western blot analysis demonstrated that alpha-MSH preserved expression of I kappa B alpha protein in vitro (glioma cells) and in vivo (brain tissue). Chloramphenicol acetyltransferase assay indicated that alpha-MSH suppresses NF-kappa B-dependent reporter gene expression induced by LPS in A-172 cells. The findings are consistent with the possibility that the anti-inflammatory action of alpha-MSH in CNS inflammation occurs via modulation of NF-kappa B activation by peptide-induced inhibition of degradation of I kappa B alpha protein. (C) 1999 Academic Press.