细胞因子对星形胶质细胞和成纤维细胞合成的神经生长因子介导的胆碱能神经营养活性的调节作用。

Cytokine regulation of nerve growth factor-mediated cholinergic neurotrophic activity synthesized by astrocytes and fibroblasts.

作者信息

Yoshida K, Kakihana M, Chen L S, Ong M, Baird A, Gage F H

机构信息

Department of Neurosciences, School of Medicine, University of California, San Diego, La Jolla 92193.

出版信息

J Neurochem. 1992 Sep;59(3):919-31. doi: 10.1111/j.1471-4159.1992.tb08331.x.

DOI:10.1111/j.1471-4159.1992.tb08331.x

PMID:1494917

Abstract

The neurotrophic activity of astrocytes and fibroblasts and its regulation by various cytokines were investigated. Astrocyte conditioned medium (ACM) enhanced the survival of neurons and the proliferation of astrocytes in embryonic cortical cultures grown in serum-free defined medium. However, these results were not affected by acidic fibroblast growth factor, interleukin-1 beta (IL-1 beta), tumor necrosis factor-alpha (TNF alpha), and transforming growth factor-beta 1. In contrast, ACM induced choline acetyltransferase expression in septal cholinergic neurons via nerve growth factor (NGF)-dependent and -independent mechanisms. However, neither acidic nor basic fibroblast growth factor is involved in this biological activity in ACM. The cytokines listed above mainly stimulate NGF-mediated cholinergic neurotrophic activity in ACM. A combination of IL-1 beta and TNF alpha significantly enhanced choline acetyltransferase activity in septal neurons co-cultured with astrocytes, and this effect was found to be mediated by NGF produced by activated astrocytes. Effects of astrocytes on GABAergic neurons were also examined. ACM was found to increase glutamate decarboxylase activity in neuronal cultures from septum in the presence of Ara-C. However, the cytokines did not enhance this activity in ACM. Moreover, a combination of IL-1 beta and TNF alpha had no effect on glutamate decarboxylase activity in septal neurons co-cultured with astrocytes. In a final set of experiments, cholinergic neurotrophic activity in skin-derived fibroblast conditioned medium (FCM) was examined. FCM was found to possess biological activity similar to that of ACM on septal neurons grown in serum-free defined medium with Ara-C. The cytokines also enhanced NGF-mediated cholinergic neurotrophic activity in FCM. Astrocytes and fibroblasts were found to possess NGF-type and non-NGF-type cholinergic neurotrophic activity, and various cytokines were found to regulate the NGF-type cholinergic neurotrophic activity in both types of cells. NGF produced by astrocytes and fibroblasts that are activated by cytokines is likely to be important for development and regeneration of NGF-sensitive neurons in the central and peripheral nervous systems.

摘要

研究了星形胶质细胞和成纤维细胞的神经营养活性及其受多种细胞因子的调控。星形胶质细胞条件培养基（ACM）可增强在无血清限定培养基中生长的胚胎皮质培养物中神经元的存活和星形胶质细胞的增殖。然而，这些结果不受酸性成纤维细胞生长因子、白细胞介素-1β（IL-1β）、肿瘤坏死因子-α（TNFα）和转化生长因子-β1的影响。相比之下，ACM通过依赖神经生长因子（NGF）和不依赖NGF的机制诱导隔区胆碱能神经元中胆碱乙酰转移酶的表达。然而，酸性和碱性成纤维细胞生长因子均不参与ACM的这种生物学活性。上述细胞因子主要刺激ACM中NGF介导的胆碱能神经营养活性。IL-1β和TNFα的组合显著增强了与星形胶质细胞共培养的隔区神经元中的胆碱乙酰转移酶活性，并且发现这种作用是由活化的星形胶质细胞产生的NGF介导的。还研究了星形胶质细胞对GABA能神经元的影响。发现在存在阿糖胞苷的情况下，ACM可增加来自隔区的神经元培养物中的谷氨酸脱羧酶活性。然而，细胞因子并未增强ACM中的这种活性。此外，IL-1β和TNFα的组合对与星形胶质细胞共培养的隔区神经元中的谷氨酸脱羧酶活性没有影响。在最后一组实验中，检测了皮肤来源的成纤维细胞条件培养基（FCM）中的胆碱能神经营养活性。发现在含有阿糖胞苷的无血清限定培养基中生长的隔区神经元上，FCM具有与ACM相似的生物学活性。细胞因子也增强了FCM中NGF介导的胆碱能神经营养活性。发现星形胶质细胞和成纤维细胞具有NGF型和非NGF型胆碱能神经营养活性，并且发现多种细胞因子可调节这两种细胞中的NGF型胆碱能神经营养活性。由细胞因子激活的星形胶质细胞和成纤维细胞产生的NGF可能对中枢和外周神经系统中对NGF敏感的神经元的发育和再生很重要。