【24h】

Inhibition of microglial superoxide anion production by isoproterenol and dexamethasone.

机译:异丙肾上腺素和地塞米松抑制小胶质超氧化物阴离子的产生。

获取原文
获取原文并翻译 | 示例
           

摘要

Microglia, like other tissue macrophages, are a component of the hypothalamic-pituitary endocrine-immune axis and, as such, are responsive to both neural and endocrine factors. Using cultured neonatal hamster microglia, we have examined the effect of isoproterenol, a beta-adrenergic agonist, and dexamethasone, a synthetic glucocorticoid, on superoxide anion production. For these experiments, microglia were pretreated with isoproterenol or dexamethasone and then induced to produce superoxide anion by exposure of the cells to phorbol myristate acetate (PMA). Our study demonstrates that the PMA-stimulated production of superoxide anion was decreased by acute (30 min) and chronic (24 h) pretreatment of the microglia with isoproterenol and was blocked by the beta-adrenergic receptor antagonist, propranolol. Since a rise in intracellular cAMP may be a prime factor in the inhibition of superoxide anion production in isoproterenol-treated cells, we used forskolin, a known activator of the adenylate cyclase in place of isoproterenol and re-investigate superoxide anion production. Short term exposures to forskolin produced a lower amount of superoxide anion than PMA-stimulated alone and, thus, mimicked the effect of isoproterenol. However, treatment with the same concentration of forskolin for 24 h prior to the induction of the NADPH oxidase did not significantly change PMA-stimulated superoxide anion production from untreated values. Thus, chronic exposure to forskolin produced a different effect than chronic exposure to isoproterenol. Isoproterenol and forskolin both increased immunoreactivity for the protein products of the early response genes, c-fos and c-jun. Pretreatment with dexamethasone for 24 h also inhibited superoxide anion production and was blocked by the protein synthesis inhibitor, cycloheximide. The simultaneous addition of varying concentrations of dexamethasone and 5 microM isoproterenol did not produce a greater inhibition in superoxide anion production than either agent alone. The down-regulation of microglial function by adrenergic agonists and by glucocorticoids provides a way in which the cytotoxicity of these immune cells can be reduced and may be a factor in the paracrine regulation of microglia.
机译:像其他组织巨噬细胞一样,小胶质细胞是下丘脑-垂体内分泌免疫轴的组成部分,因此对神经和内分泌因子均具有反应。使用培养的仓鼠小胶质细胞,我们检查了β-肾上腺素能激动剂异丙肾上腺素和合成糖皮质激素地塞米松对超氧阴离子产生的影响。对于这些实验,小胶质细胞用异丙肾上腺素或地塞米松预处理,然后通过将细胞暴露于佛波肉豆蔻酸酯乙酸酯(PMA)诱导产生超氧化物阴离子。我们的研究表明,用异丙肾上腺素对小胶质细胞进行急性(30分钟)和慢性(24 h)预处理会降低PMA刺激的超氧阴离子生成,并被β-肾上腺素受体拮抗剂普萘洛尔阻断。由于细胞内cAMP的升高可能是抑制异丙肾上腺素处理的细胞中超氧阴离子产生的主要因素,因此我们使用福斯高林(forskolin)(一种已知的腺苷酸环化酶激活剂)代替了异丙肾上腺素,并重新研究了超氧阴离子的产生。短期暴露于福斯高灵比单独使用PMA刺激产生的过氧化物负离子量少,因此模仿了异丙肾上腺素的作用。但是,在诱导NADPH氧化酶之前用相同浓度的福司可林处理24小时,未从未处理的值显着改变PMA刺激的超氧阴离子的产生。因此,长期暴露于福斯高林可产生与慢性暴露于异丙肾上腺素不同的效果。异丙肾上腺素和佛司可林都提高了早期反应基因c-fos和c-jun蛋白产物的免疫反应性。地塞米松预处理24小时也抑制了超氧阴离子的产生,并被蛋白质合成抑制剂环己酰亚胺阻断。同时添加不同浓度的地塞米松和5 microM异丙肾上腺素对超氧阴离子的产生没有比任何一种单独的药剂产生更大的抑制作用。肾上腺素能激动剂和糖皮质激素对小胶质细胞功能的下调提供了一种途径,可以减少这些免疫细胞的细胞毒性,并且可能是小胶质旁分泌调节的一个因素。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号