Understanding the dynamics of Toll-like Receptor 5 response to flagellin and its regulation by estradiol

CABALLERO, I, BOYD, J, ALMINANÃ, C, SÁNCHEZ-LÓPEZ, JA, BASATVAT, Shaghayegh, MONTAZERI, M, MASLEHAT LAY, N, ELLIOTT, S, SPILLER, DG, WHITE, MRH and FAZELI, A (2017). Understanding the dynamics of Toll-like Receptor 5 response to flagellin and its regulation by estradiol. Scientific Reports, 7 (1), p. 40981.

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Official URL: https://www.nature.com/articles/srep40981
Link to published version:: https://doi.org/10.1038/srep40981
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    Abstract

    © 2017 The Author(s). Toll-like receptors (TLRs) are major players of the innate immune system. Once activated, they trigger a signalling cascade that leads to NF-ΰ B translocation from the cytoplasm to the nucleus. Single cell analysis shows that NF-ΰ B 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-k B translocation into the nucleus that resulted in high NF-k B transcription activity. The overall magnitude of NF-k B transcription activity was not influenced by the duration of the stimulus. No significant changes are observed in the dynamics of NF-k B translocation to the nucleus when MCF7 cells are incubated with estradiol. However, estradiol significantly decreased NF-k B 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-k B transcription factor.

    Item Type: Article
    Uncontrolled Keywords: Estradiol; Estrogens; Flagellin; Gene Expression Regulation; Humans; MCF-7 Cells; NF-kappa B; Protein Transport; Signal Transduction; Single-Cell Analysis; Toll-Like Receptor 5; Transcription, Genetic; Humans; Estradiol; Flagellin; NF-kappa B; Estrogens; Signal Transduction; Transcription, Genetic; Gene Expression Regulation; Protein Transport; Toll-Like Receptor 5; Single-Cell Analysis; MCF-7 Cells
    Identification Number: https://doi.org/10.1038/srep40981
    Page Range: p. 40981
    SWORD Depositor: Symplectic Elements
    Depositing User: Symplectic Elements
    Date Deposited: 31 Jan 2020 11:40
    Last Modified: 31 Jan 2020 11:45
    URI: http://shura.shu.ac.uk/id/eprint/25004

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