Coordinate NF-κB and STAT1 activation promotes development of myeloid type 1 dendritic cells
Coordinate NF-κB and STAT1 activation promotes development of myeloid type 1 dendritic cells
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DOI：
10.1111/j.1365-3083.2007.02068.x
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发表时间：
2008-03-01
影响因子：
3.7
通讯作者：
Lotze, M. T.
中科院分区：
文献类型：
--
作者：
Vakkila, J.;Demarco, R. A.;Lotze, M. T.
NF-κ B和STAT 1在炎症级联反应的启动中起关键作用。使用半自动成像细胞术和荧光抗体，我们筛选了几个因素的能力，诱导核转位的RelA/NF-κ B和STAT 1的单核细胞衍生的树突状细胞（DC）的子集。提供了IL-1、LPS、CD 40 L、IFN-γ和IFN-α刺激反应的详细动力学和剂量反应研究。结果与以下观点一致，即在分化培养起始时同时激活STAT 1和NF-κ B途径是DC有效引发IL-12产生所必需的。DC的成熟导致特征性NF-κ B和STAT 1分布和反应模式。在静息阶段，在IFN-γ存在下分化的DC显示持续的STAT激活，并保持对LPS的响应。相反，补充PGE（2）的DC可以通过对LPS和IFN-γ的可忽略的反应和对CD 40 L的显著的NF-κ B反应来表征。STAT 1通路在补充PGE（2）的细胞中被抑制。我们的结论是STAT 1和NF-κ B B在髓样DC中的核移位的幅度和时间动力学与IL-12 p70的产生相关，并且依赖于刺激因子的性质和细胞的极化状态。
NF-kappa B and STAT1 are critically involved in the initiation of the inflammatory cascade. Using semi-automated imaging cytometry and fluorescent antibodies, we screened several factors for their ability to induce nuclear translocation of RelA/NF-kappa B and STAT1 in subsets of monocyte-derived dendritic cells (DC). Detailed kinetics and dose-response studies are presented for IL-1-, LPS-, CD40L-, IFN-gamma- and IFN-alpha-stimulated responses. The results are consistent with the notion that simultaneous activation of both STAT1 and NF-kappa B pathways at the initiation of differentiation culture is required for efficient priming of IL-12 production by DC. Maturation of DC led to characteristic NF-kappa B and STAT1 distribution and response patterns. During the resting stage, DC differentiated under the presence of IFN-gamma showed sustained STAT activation and remained responsive to LPS. By contrast, PGE(2)-supplemented DC could be characterized by negligible responses to LPS and IFN-gamma and a remarkable NF-kappa B response to CD40L. STAT1 pathway was suppressed in PGE(2)-supplemented cells. We conclude that the magnitude and temporal kinetics of the nuclear shift of STAT1 and NF-kappa B in myeloid DC are associated with IL-12p70 production and are dependent on the nature of the stimulating factors and the polarization state of cells.