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转化生长因子-β1抑制血清和生长因子诱导的大鼠星形胶质细胞增殖。

Transforming growth factor-beta 1 inhibits the proliferation of rat astrocytes induced by serum and growth factors.

作者信息

Vergeli M, mazzanti B, Ballerini C, Gran B, Amaducci L, Massacesi L

机构信息

Dipartimento Scienze Neurologiche e Psichiatriche, Università degli Studi di Firenze, Italy.

出版信息

J Neurosci Res. 1995 Jan 1;40(1):127-33. doi: 10.1002/jnr.490400114.

DOI:10.1002/jnr.490400114
PMID:7714920
Abstract

A number of cytokines and growth factors may affect astrocyte proliferation and functions. Transforming growth factor-beta 1 (TGF-beta 1) is a pleiotropic cytokine which exerts multiple effects on growth and differentiation of different cell types. TGF-beta 1 is present in low amounts in the normal brain. TGF-beta 1 gene expression, however, is increased in the central nervous system (CNS) in several pathological conditions. In this study we examined the in vitro effects of TGF-beta 1 on the proliferative response of rat astrocytes to serum and growth factors. Astrocyte cultures were established from the cerebellum and cortex of newborn Lewis rats. The proliferative response of these cultures to serum and growth factors [platelet-derived growth factor (PDGF), basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), insulin-like growth factor 1 (IGF-1), IGF-2, interleukin 1 (IL-1)] was studied by [3H]-thymidine incorporation test in the presence or absence of TGF-beta 1. TGF-beta 1 significantly inhibited the proliferative response of astrocyte cultures to both autologous and heterologous serum. In addition, a strong inhibition of bFGF-, EGF-, and PDGF-induced proliferation was observed. The effect of TGF-beta 1 on the proliferative response to IL-1 was less evident but still significant. No effect was observed when TGF-beta 1 was added to IGF-1 and IGF-2 stimulated cultures. These data confirm previous reports showing a down-regulating activity of TGF-beta on astrocyte proliferation and suggest that this cytokine may play physiological and pharmacological roles in the regulation of reactive astrocytosis in the CNS.

摘要

多种细胞因子和生长因子可能影响星形胶质细胞的增殖和功能。转化生长因子-β1(TGF-β1)是一种多效性细胞因子,对不同细胞类型的生长和分化具有多种作用。在正常大脑中,TGF-β1含量较低。然而,在几种病理情况下,TGF-β1基因表达在中枢神经系统(CNS)中会增加。在本研究中,我们检测了TGF-β1对大鼠星形胶质细胞对血清和生长因子增殖反应的体外影响。从新生Lewis大鼠的小脑和皮质建立星形胶质细胞培养物。通过[3H] - 胸腺嘧啶核苷掺入试验,在存在或不存在TGF-β1的情况下,研究这些培养物对血清和生长因子[血小板衍生生长因子(PDGF)、碱性成纤维细胞生长因子(bFGF)、表皮生长因子(EGF)、胰岛素样生长因子1(IGF-1)、IGF-2、白细胞介素1(IL-1)]的增殖反应。TGF-β1显著抑制星形胶质细胞培养物对自体和异体血清的增殖反应。此外,观察到对bFGF、EGF和PDGF诱导的增殖有强烈抑制作用。TGF-β1对IL-1诱导的增殖反应的影响不太明显,但仍然显著。当将TGF-β1添加到IGF-1和IGF-2刺激的培养物中时,未观察到影响。这些数据证实了先前关于TGF-β对星形胶质细胞增殖具有下调活性的报道,并表明这种细胞因子可能在中枢神经系统反应性星形胶质细胞增生的调节中发挥生理和药理作用。

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