Production of hemolymphopoietic cytokines (IL-6, IL-8, colony-stimulating factors) by normal human astrocytes in response to IL-1 beta and tumor necrosis factor-alpha.
Production of hemolymphopoietic cytokines (IL-6, IL-8, colony-stimulating factors) by normal human astrocytes in response to IL-1 beta and tumor necrosis factor-alpha.
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DOI：
10.4049/jimmunol.149.7.2358
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发表时间：
1992-10
影响因子：
4.4
通讯作者：
F. Aloisi;A. Carè;G. Borsellino;P. Gallo;S. Rosa;Anna Bassani;A. Cabibbo;U. Testa;G. Levi;C. Peschle
中科院分区：
文献类型：
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作者：
F. Aloisi;A. Carè;G. Borsellino;P. Gallo;S. Rosa;Anna Bassani;A. Cabibbo;U. Testa;G. Levi;C. Peschle
富含星形胶质细胞的群体是从人胚胎脑中建立的，分析了它们合成可能与大脑炎症和免疫机制相关的细胞因子的能力。未刺激的星形胶质细胞不分泌显著的IL-6、IL-8、巨噬细胞CSF（M-CSF）、粒细胞-巨噬细胞CSF（GM-CSF）或粒细胞-CSF（G-CSF），如通过特异性ELISA和/或生物测定所确定的。除M-CSF mRNA外，在未刺激的星形胶质细胞中未检测到上述因子的转录物。在人星形胶质细胞暴露于IL-1 β时，检测到高水平的IL-6、IL-8、M-CSF、G-CSF和GM-CSF mRNA;此外，证明了所有上述细胞因子的主动分泌。TNF-α也能够刺激IL-6、IL-8、M-CSF、GM-CSF和G-CSF的合成和分泌，但通常不如IL-1 β有效。在未刺激的或经苦参碱处理的星形胶质细胞中未检测到IL-3 mRNA或蛋白。在未刺激的星形胶质细胞中未检测到IL-1 α和IL-1 β mRNA和蛋白，但在用TNF-α/IL-1 β刺激后以非常少量存在。在主要含有未分化的神经元/神经胶质祖细胞的早期原代培养物中，IL-1 β或TNF-α未诱导IL-6、M-CSF、GM-CSF、G-CSF或IL-8。这些研究首次证明了在培养物中由IL-1 β和TNF-α刺激的正常人星形胶质细胞产生多种细胞因子。人星形胶质细胞合成和释放对血淋巴细胞有活性的细胞因子的能力支持了这样的概念，即这些细胞在各种脑病理中的炎症和免疫反应的调节中发挥重要作用。
Astrocyte-enriched populations were established from human embryonic brain analyzed for their ability to synthesize cytokines potentially relevant for mechanisms of inflammation and immunity in the brain. Unstimulated astrocytes did not secrete significant IL-6, IL-8, macrophage CSF (M-CSF), granulocyte-macrophage CSF (GM-CSF), or granulocyte-CSF (G-CSF), as determined by specific ELISA and/or bioassay. With the exception of M-CSF mRNA, transcripts for the above factors were not detected in unstimulated astrocytes. On exposure of human astrocytes to IL-1 beta, high levels of IL-6, IL-8, M-CSF, G-CSF, and GM-CSF mRNAs were detected; moreover, active secretion of all the above cytokines was demonstrated. TNF-alpha was also able to stimulate IL-6, IL-8, M-CSF, GM-CSF, and G-CSF synthesis and secretion, but was generally less potent than IL-1 beta. No IL-3 mRNA or protein was detected in unstimulated or cytokine-treated astrocytes. IL-1 alpha and IL-1 beta mRNAs and proteins were not detected in unstimulated astrocytes, but were present in very small amounts after stimulation with TNF-alpha/IL-1 beta. No IL-6, M-CSF, GM-CSF, G-CSF, or IL-8 were induced by IL-1 beta or TNF-alpha in early primary cultures, which mainly contain undifferentiated neuronal/glial progenitor cells. These studies demonstrate for the first time the production of multiple cytokines by normal human astrocytes stimulated in culture by IL-1 beta and TNF-alpha. The capacity of human astrocytes to synthesize and release cytokines active on hemolymphopoietic cells supports the concept that these cells play an important role in the regulation of inflammatory and immune responses in a variety of brain pathologies.