Regulation of interleukin-6 gene expression in brain of aged mice by nuclear factor κB
Regulation of interleukin-6 gene expression in brain of aged mice by nuclear factor κB
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DOI：
10.1016/s0165-5728(01)00316-2
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发表时间：
2001-07-02
影响因子：
3.3
通讯作者：
Johnson, RW
中科院分区：
文献类型：
--
作者：
Ye, SM;Johnson, RW
白细胞介素-6（IL-6）在老龄小鼠脑中升高。本研究的目的是确定核因子kappaB（NF kappaB）与IL-6启动子的结合是否与脑IL-6的年龄相关性增加有关。在最初的研究中，年龄对脑中IL-6的影响得到了验证，因为与成年和幼年小鼠相比，老年小鼠脑中的IL-6蛋白增加。竞争性RT-PCR显示，IL-6 mRNA的浓度在老年脑中至少是成人脑的4倍。接下来，在1个月、6个月和24个月大的小鼠的脑中测定转录因子NF κ B与IL-6启动子的结合。电泳迁移率变动分析显示，与成人和青少年脑相比，老年脑中NF κ B活性增加。此外，从老年小鼠培养的胶质细胞显示更多的NF κ B DNA结合活性和更多的IL-6 mRNA和蛋白表达比成年人的胶质细胞。然而，在kappaB诱饵存在的情况下孵育来自老年小鼠的神经胶质细胞抑制了年龄的这些影响。在老龄小鼠侧脑室注射kappaB诱骗物可降低脑内NF-κ B活性和IL-6 mRNA及蛋白表达。这些结果表明，NF κ B的DNA结合活性在老年小鼠的脑中增加，并且至少一个结果是IL-6的表达增加。(C)2001爱思唯尔科技有限公司。保留所有权利。
Interleukin-6 (IL-6) is increased in brain of aged mice. The purpose of this study was to determine if binding of nuclear factor kappaB (NF kappaB) to the IL-6 promoter is responsible for the age-related increase in brain IL-6. In an initial study, the effect of age on IL-6 in brain was verified as IL-6 protein was increased in brain of aged mice compared to adult and juvenile mice. Competitive RT-PCR showed that IL-6 mRNA concentration was at least 4-fold higher in aged brain compared to adult brain. Next, binding of the transcription factor NF kappaB to the IL-6 promoter in brains of 1-, 6-, and 24-month-old mice was determined. Electrophoretic mobility shift assay showed that NF kappaB activity was increased in aged brain compared to adult and juvenile brain. Moreover, glial cells cultured from aged mice showed more NF kappaB DNA-binding activity and more IL-6 mRNA and protein expression than glia from adults. However, incubating glia from aged mice in the presence Of kappaB decoy inhibited these effects of age. The same was observed in vivo as intracerebroventricular injection Of kappaB decoy in aged mice decreased NF kappaB activity and IL-6 mRNA and protein in brain. These results show that the DNA-binding activity of NF kappaB is increased in the brain of aged mice and that at least one consequence is increased expression of IL-6. (C) 2001 Elsevier Science B.V. All rights reserved.