REGULATION BY INTERLEUKIN-1 OF NERVE GROWTH-FACTOR SECRETION AND NERVE GROWTH-FACTOR MESSENGER-RNA EXPRESSION IN RAT PRIMARY ASTROGLIAL CULTURES

REGULATION BY INTERLEUKIN-1 OF NERVE GROWTH-FACTOR SECRETION AND NERVE GROWTH-FACTOR MESSENGER-RNA EXPRESSION IN RAT PRIMARY ASTROGLIAL CULTURES
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DOI:
10.1111/j.1471-4159.1991.tb08197.x
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发表时间:
1991-02-01
影响因子:
4.7
通讯作者:
WISE, BC
WISE, BC
中科院分区:
医学2区
文献类型:
--
作者:
CARMANKRZAN, M;VIGE, X;WISE, BC

文献摘要

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新生大鼠皮质星形胶质细胞原代培养物含有低水平的神经生长因子(NGF)(约2 pg/mg蛋白),但在培养液中可分泌大量的NGF(约540 pg/mg细胞蛋白/38小时孵育)。与白细胞介素-1 (IL-1)孵育星形胶质细胞后,细胞内NGF的含量和分泌量增加了约3倍。相比之下,小脑星形胶质细胞分泌大量的NGF,并且分泌也受到IL-1的刺激。IL-1对脑皮层星形胶质细胞的刺激作用具有剂量和时间依赖性。IL-1对NGF分泌的半极大和极大刺激浓度分别为1和10 U/ml。IL-1 (10 U/ml)诱导的NGF分泌在孵育38 h后达到最大值。在无Ca2+条件下,NGF的基础分泌减少了约50%;然而,无论Ca2+存在与否,IL-1对NGF分泌的刺激百分比是相同的。IL-1的刺激作用是特异性的,因为其他胶质生长因子和细胞因子在刺激皮层星形胶质细胞分泌NGF方面几乎无效。IL-1处理也使细胞NGF mRNA含量增加两倍。结果表明,IL-1特异性触发一系列事件,独立于细胞生长,调节星形胶质细胞NGF mRNA含量和NGF分泌。
Primary cultures of neonatal rat cortical astrocytes contain low cellular levels (about 2 pg/mg of protein) of nerve growth factor (NGF), but secrete significant amounts of NGF into the culture medium (about 540 pg of NGF/mg of cell protein/38-h incubation). Incubation of astrocytes with interleukin-1 (IL-1) increased the cellular content of NGF and the amount secreted by about threefold. In comparison, cerebellar astrocytes secreted significant amounts of NGF, and the secretion was also stimulated by IL-1. The stimulatory action of IL-1 on astrocytes prepared from cortex was dose- and time-dependent. Concentrations of IL-1 causing half-maximal and maximal stimulation of NGF secretion were 1 and 10 U/ml, respectively. Maximal NGF secretion induced by IL-1 (10 U/ml) was seen following 38 h of incubation. The basal secretion of NGF was reduced by about 50% under Ca2+-free conditions; however, the percent stimulation of NGF secretion by IL-1 was the same in the absence or presence of Ca2+. The stimulatory action of IL-1 was specific, because other glial growth factors and cytokines were almost ineffective in stimulating NGF secretion from cortial astroglial cells. IL-1 treatment also increased cellular NGF mRNA content twofold. The results indicate that IL-1 specifically triggers a cascade of events, independent of cell growth, which regulate NGF mRNA content and NGF secretion by astrocytes.