Tumor necrosis factor-alpha production by astrocytes. Induction by lipopolysaccharide, IFN-gamma, and IL-1 beta.
Tumor necrosis factor-alpha production by astrocytes. Induction by lipopolysaccharide, IFN-gamma, and IL-1 beta.
复制标题
DOI：
10.4049/jimmunol.144.8.2999
复制
发表时间：
1990-04
影响因子：
4.4
通讯作者：
I. Chung;E. Benveniste
中科院分区：
文献类型：
--
作者：
I. Chung;E. Benveniste
星形胶质细胞具有分泌或响应多种细胞因子的能力，包括 IL-1、IL-6、IL-3 和 TNF-α。在这项研究中，我们检查了星形胶质细胞响应各种生物刺激而分泌 TNF-α 的能力，特别是 IL-1 和 IFN-γ 等细胞因子，已知这些细胞因子在与炎症相关的神经系统疾病期间存在于中枢神经系统中。大鼠星形胶质细胞不会持续产生 TNF-α，但能够响应 LPS 分泌 TNF-α，并且可以通过 IFN-γ 引发对次优剂量的 LPS 做出反应。单独的IFN-γ和IL-1β不会诱导TNF-α的产生，然而，IFN-γ和IL-1β的联合治疗对星形胶质细胞TNF-α的产生产生显着的协同作用。由 IFN-γ/LPS 或 IFN-γ/IL-1β 联合治疗诱导的星形胶质细胞 TNF-α 蛋白产生以剂量和时间依赖性方式发生，并且似乎需要由 IFN-γ 启动的“启动信号”，然后使星形胶质细胞对次优剂量的 LPS 或 IL-1β 做出反应。通过添加抗大鼠 IFN-γ 抗体，可以抑制 IFN-γ/LPS 刺激产生的星形胶质细胞 TNF-α，而 IFN-γ/IL-1 诱导的 TNF-α 产生则受到 IFN-γ 或 IL-1 β 抗体的抑制。与小鼠巨噬细胞来源的 TNF-α 反应的多克隆抗血清中和了 IFN-γ/LPS 和 IFN-γ/IL-1β 诱导的星形胶质细胞 TNF-α 的细胞毒性，证明了这两种来源的 TNF-α 之间的相似性。我们认为，星形胶质细胞产生的 TNF-α 可能在增强脑内免疫反应和炎症脱髓鞘方面发挥关键作用，因为它对胶质细胞（如少突胶质细胞和星形胶质细胞本身）具有多种功能作用。
Astrocytes have the capacity to secrete or respond to a variety of cytokines including IL-1, IL-6, IL-3, and TNF-alpha. In this study, we have examined the capacity of astrocytes to secrete TNF-alpha in response to a variety of biologic stimuli, particularly cytokines such as IL-1 and IFN-gamma, which are known to be present in the central nervous system during neurologic diseases associated with inflammation. Rat astrocytes do not constitutively produce TNF-alpha, but have the ability to secrete TNF-alpha in response to LPS, and can be primed by IFN-gamma to respond to a suboptimal dose of LPS. IFN-gamma and IL-1 beta alone do not induce TNF-alpha production, however, the combined treatment of IFN-gamma and IL-1 beta results in a striking synergistic effect on astrocyte TNF-alpha production. Astrocyte TNF-alpha protein production induced by a combined treatment of either IFN-gamma/LPS or IFN-gamma/IL-1 beta occurs in a dose- and time-dependent manner, and appears to require a "priming signal" initiated by IFN-gamma, which then renders the astrocyte responsive to either a suboptimal dose of LPS or IL-1 beta. Astrocyte TNF-alpha production by IFN-gamma/LPS stimulation can be inhibited by the addition of anti-rat IFN-gamma antibody, whereas IFN-gamma/IL-1-induced TNF-alpha production is inhibited by antibody to either IFN-gamma or IL-1 beta. Polyclonal antisera reactive with mouse macrophage-derived TNF-alpha neutralized the cytotoxicity of IFN-gamma/LPS and IFN-gamma/IL-1 beta-induced astrocyte TNF-alpha, demonstrating similarities between these two sources of TNF-alpha. We propose that astrocyte-produced TNF-alpha may have a pivotal role in augmenting intracerebral immune responses and inflammatory demyelination due to its diverse functional effects on glial cells such as oligodendrocytes and astrocytes themselves.