AUTOCRINE AND PARACRINE REGULATION OF ASTROCYTE FUNCTION BY TRANSFORMING GROWTH-FACTOR-BETA
AUTOCRINE AND PARACRINE REGULATION OF ASTROCYTE FUNCTION BY TRANSFORMING GROWTH-FACTOR-BETA
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DOI：
10.1016/0165-5728(92)90185-n
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发表时间：
1992-07-01
影响因子：
3.3
通讯作者：
WAHL, SM
中科院分区：
文献类型：
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作者：
MORGANTIKOSSMANN, MC;KOSSMANN, T;WAHL, SM
最近的证据表明，星形胶质细胞具有广泛的功能，通常归因于免疫系统的细胞，其对于维持中枢神经系统（CNS）中平衡的稳态环境至关重要。此外，已知这些细胞通过分泌细胞因子如转化生长因子-β（TGF-β）参与CNS内的炎症事件。在这项研究中，我们研究了TGF-β影响星形胶质细胞功能的能力。TGF-β-1 mRNA在体外由星形胶质细胞组成性表达，当用外源性TGF-β-1刺激培养物时，可以显示该mRNA表达的增加，这表明自分泌和旁分泌调节。在体外试验中，TGF-β-1以剂量依赖性方式对星形胶质细胞具有趋化性，并抑制星形胶质细胞增殖。这些结果表明TGF-β-1的信号转导促使研究探索分离的星形胶质细胞群体上的受体-配体相互作用。在受体结合试验中，我们证明星形胶质细胞似乎表达三种不同的TGF-β受体亚型，每个细胞有近10000个受体。因此，TGF-β可能在调节星形胶质细胞功能中发挥重要作用，星形胶质细胞功能对脑内免疫应答的演变至关重要，包括CNS内局部炎症部位的神经胶质细胞的募集和活化。
Recent evidence indicates that astrocytes have a wide range of functions, usually attributed to cells of the immune system, which are critical for maintaining a balanced homeostatic environment in the central nervous system (CNS). Moreover, these cells are known to participate in inflammatory events within the CNS by secreting cytokines such as transforming growth factor-beta (TGF-beta). In this study we have investigated the ability of TGF-beta to influence astrocyte functions. TGF-beta-1 mRNA is constitutively expressed by astrocytes in vitro, and when cultures are stimulated with exogenous TGF-beta-1 an increase in the expression of this mRNA can be shown, suggesting both autocrine and paracrine regulation. In in vitro assays, TGF-beta-1 is chemotactic for astrocytes in a dose-dependent fashion and inhibits astrocyte proliferation. These results indicating signal transduction by TGF-beta-1-prompted studies to explore receptor-ligand interactions on isolated astrocyte populations. In a receptor binding assay, we demonstrate that astrocytes appear to express three distinct TGF-beta receptor subtypes with nearly 10000 receptors per cell. Thus, TGF-beta may play an important role in regulating astrocyte functions pivotal to the evolution of intracerebral immune responses including recruitment and activation of glial cells at local inflammatory sites within the CNS.