Cytokine regulation of CC and CXC chemokine expression by human astrocytes
Cytokine regulation of CC and CXC chemokine expression by human astrocytes
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DOI：
10.3109/13550289909029749
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发表时间：
1999-02-01
影响因子：
3.2
通讯作者：
Benveniste, EN
中科院分区：
文献类型：
--
作者：
Oh, JW;Schwiebert, LM;Benveniste, EN
趋化因子构成了一个分泌蛋白大家族，充当白细胞的趋化剂和激活剂。星形胶质细胞是中枢神经系统 (CNS) 中的主要神经胶质细胞类型，是患病大脑内趋化因子产生的来源。因此，我们检查了用多种刺激（包括 LPS、TNF-α、IFN-γ 和 IL-1β）处理的人星形胶质瘤细胞系和原代人星形胶质细胞产生的趋化因子。此外。测试了 IL-6 与可溶性 IL-6 受体 (sIL-6R) 以及杂合 IL-6 (H-IL-6)（一种 sIL-6R 和 IL-6 的高活性融合蛋白）诱导趋化因子表达的能力。本文提出的发现表明，人星形胶质瘤细胞系和原代人星形胶质细胞响应TNF-α和IL-1β表达CXC趋化因子IP-10和IL-8以及CC趋化因子MCP-1和RANTES。 IFN-γ诱导IP-10的表达，但不诱导IL-8、MCP-1或RANTES的表达。令人惊讶的是，IL-6/sIL-6R和H-IL-6对这些细胞中的趋化因子表达几乎没有影响或没有影响。还检查了 TGF-β 对人星形胶质瘤细胞系和星形胶质细胞中趋化因子表达的影响。单独使用 TGF-β 对 RANTES、MCP-1 和 IL-8 表达影响很小或没有影响；然而，TGF-β 与 TNF-α 协同增强星形胶质瘤细胞和原代星形胶质细胞中的 MCP-1 表达。在人星形胶质瘤细胞中观察到 TGF-β 对 TNF-α 和 IL-1β 诱导的 RANTES 和 IL-8 表达的抑制作用。相反，TGF-β增强TNF-α和IL-1β诱导人星形胶质细胞产生IL-8。这些发现证明了多效性细胞因子 TGF-β 的趋化因子调节的复杂模式，具有增强和抑制作用。
Chemokines constitute a large family of secreted proteins that function as chemoattractants and activators of leukocytes. Astrocytes, the major glial cell type in the central nervous system (CNS), are a source of chemokine production within diseased brain. As such, we have examined the production of chemokines by human astroglioma cell lines and primary human astrocytes treated with a variety of stimuli, including LPS, TNF-alpha, IFN-gamma and IL-1 beta. In addition. IL-6 in conjunction with the soluble IL-6 receptor (sIL-6R), and hybrid IL-6 (H-IL-6), a highly active fusion protein of sIL-6R and IL-6, were tested for their ability to induce chemokine expression. The findings presented herein demonstrate that both human astroglioma cell lines and primary human astrocytes express the CXC chemokines IP-10 and IL-8 and the CC chemokines MCP-1 and RANTES in response to TNF-alpha and IL-1 beta. IFN-gamma induced the expression of IP-10, but not of IL-8, MCP-1 or RANTES. Surprisingly, IL-6/sIL-6R and H-IL-6 had little or no effect on chemokine expression in these cells. The effect of TGF-beta on chemokine expression In human astroglioma cell lines and astrocytes was also examined. TGF-beta alone had little or no effect on RANTES, MCP-1 and IL-8 expression; however, TGF-beta synergized with TNF-alpha to enhance MCP-1 expression in both astroglioma cells and primary astrocytes. An inhibitory effect of TGF-beta on TNF-alpha and IL-1 beta induced RANTES and IL-8 expression was observed in human astroglioma cells. In contrast, TGF-beta enhanced TNF-alpha and IL-1 beta induction of IL-8 production by human astrocytes. These findings document a complex pattern of chemokine regulation by the pleiotropic cytokine TGF-beta with both enhancing and inhibitory effects.