Understanding the dynamics of Toll-like Receptor 5 response to flagellin and its regulation by estradiol.
Understanding the dynamics of Toll-like Receptor 5 response to flagellin and its regulation by estradiol.
复制标题
了解Toll样受体5对鞭毛蛋白的反应及其对雌二醇的调节的动力学。
DOI：
10.1038/srep40981
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发表时间：
2017-01-23
影响因子：
4.6
通讯作者：
Fazeli A
中科院分区：
文献类型：
--
作者：
Caballero I;Boyd J;Almiñana C;Sánchez-López JA;Basatvat S;Montazeri M;Maslehat Lay N;Elliott S;Spiller DG;White MR;Fazeli A
Toll样受体（TLR）是先天免疫系统的主要参与者。一旦被激活，它们触发信号级联，导致NF-κ B从细胞质易位到细胞核。单细胞分析表明NF-κ B信号动力学是转录调控的关键决定因素。此外，先天免疫应答的结果也受到TLR和雌激素信号传导之间的串扰的影响。在这里，我们的特点TLR5信号的动力学，负责识别鞭毛细菌，和雌二醇在其信号在单细胞水平诱导的变化。在MCF 7细胞中TLR5的激活诱导了NF-κ B单次和持续的核转位，导致高NF-κ B转录活性。NF-κ B转录活性的总体幅度不受刺激持续时间的影响。当MCF 7细胞与雌二醇孵育时，未观察到NF-κ B向核移位的动力学的显著变化。然而，雌二醇显著降低NF-κ B的转录活性，而增加TLR5介导的AP-1的转录。雌二醇对转录活性的影响依赖于雌激素受体的激活。这种微调似乎主要发生在核转录水平，而不是影响NF-κ B转录因子的易位。
Toll-like receptors (TLRs) are major players of the innate immune system. Once activated, they trigger a signalling cascade that leads to NF-κB translocation from the cytoplasm to the nucleus. Single cell analysis shows that NF-κB signalling dynamics are a critical determinant of transcriptional regulation. Moreover, the outcome of innate immune response is also affected by the cross-talk between TLRs and estrogen signalling. Here, we characterized the dynamics of TLR5 signalling, responsible for the recognition of flagellated bacteria, and those changes induced by estradiol in its signalling at the single cell level. TLR5 activation in MCF7 cells induced a single and sustained NF-κB translocation into the nucleus that resulted in high NF-κB transcription activity. The overall magnitude of NF-κB transcription activity was not influenced by the duration of the stimulus. No significant changes are observed in the dynamics of NF-κB translocation to the nucleus when MCF7 cells are incubated with estradiol. However, estradiol significantly decreased NF-κB transcriptional activity while increasing TLR5-mediated AP-1 transcription. The effect of estradiol on transcriptional activity was dependent on the estrogen receptor activated. This fine tuning seems to occur mainly in the nucleus at the transcription level rather than affecting the translocation of the NF-κB transcription factor.