Bacterial lipopolysaccharide, TNF-α, and calcium ionophore under serum-free conditions promote rapid dendritic cell-like differentiation in CD14+ monocytes through distinct pathways that activate NF-κB
Bacterial lipopolysaccharide, TNF-α, and calcium ionophore under serum-free conditions promote rapid dendritic cell-like differentiation in CD14+ monocytes through distinct pathways that activate NF-κB
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DOI：
10.4049/jimmunol.165.7.3647
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发表时间：
2000-10-01
影响因子：
4.4
通讯作者：
Rice, NR
中科院分区：
文献类型：
--
作者：
Lyakh, LA;Koski, GK;Rice, NR
为了促进髓样树突状细胞（DC）分化相关信号通路的研究，我们开发了一种无血清培养系统，其中人CD 14（+）外周血单核细胞响应细菌LPS、TNF-α或钙离子载体（CI）而快速分化。在48-96小时内，取决于诱导剂，细胞获得许多免疫表型、形态、功能、和DC的分子特性。然而，这些试剂使用的信号传导途径存在显著差异，因为1）LPS诱导的而非CI诱导的DC分化需要TNF-α产生; 2）环孢菌素A抑制CI诱导的分化，但不抑制LPS诱导的分化。然而，所有三种诱导剂均激活NF-κ B家族转录因子的成员，包括Rein，这表明尽管上游元件不同，但信号通路都涉及NF-κ B B。在这份报告中，我们还证明并解释了两种观察到的RelB蛋白形式，并表明RelB可以通过钙依赖性和环孢菌素A敏感性通路在髓样细胞中直接或间接诱导。
To facilitate the study of signaling pathways involved in myeloid dendritic cell (DC) differentiation, we have developed a serum-free culture system in which human CD14(+) peripheral blood monocytes differentiate rapidly in response to bacterial LPS, TNF-alpha, or calcium ionophore (CI), Within 48-96 h, depending on the inducing agent, the cells acquire many immunophenotypical, morphological, functional, and molecular properties of DC. However, there are significant differences in the signaling pathways used by these agents, because 1) LPS-induced, but not CI-induced, DC differentiation required TNF-alpha production; and 2) cyclosporin A inhibited differentiation induced by CI, but not that induced by LPS, Nevertheless, all three inducing agents activated members of the NF-kappa B family of transcription factors, including Rein, suggesting that despite differences in upstream elements, the signaling pathways all involve NF-kappa B, In this report we also demonstrate and offer an explanation for two observed forms of the RelB protein and show that RelB can be induced in myeloid cells, either directly or indirectly, through a calcium-dependent and cyclosporin A-sensitive pathway.