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Modulation of Stimulator of Interferon Genes (STING) Expression by Interferon-γ in Human Keratinocytes

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Abstract

Infection of microbial pathogen triggers the innate immune system, and the induction of interferons (IFNs) play a vital role in host antiviral response. Stimulator of interferon genes (STING) was identified as a crucial regulator of the DNA sensing pathway, and activates both nuclear factor-κB and interferon regulatory factor 3 transcription pathways to evoke IFNs production. In this study, we studied the upregulation of STING mRNA expression, induced by IFN-γ in human keratinocytes (HaCaT). STING promoter assays clarified that a gamma-activated sequence (GAS), located at − 7 to − 15-bp, is required for IFN-γ-upregulated promoter activity. Furthermore, an electrophoretic mobility shift assay showed that signal transducers and activators of transcription 1 (STAT1) attach to the GAS motif on the human STING promoter region. This indicates that IFN-γ/Janus kinases/STAT1 signaling is essential for the STING upregulation in human keratinocytes.

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Acknowledgements

We thank Ms. Yukiko Tamura and Ikuko Takahashi for their technical assistance. This work was supported by KAKENHI (26461675).

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Correspondence to Yasushi Matsuzaki.

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Nishikawa, Y., Matsuzaki, Y., Kimura, K. et al. Modulation of Stimulator of Interferon Genes (STING) Expression by Interferon-γ in Human Keratinocytes. Biochem Genet 56, 93–102 (2018). https://doi.org/10.1007/s10528-017-9832-7

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  • DOI: https://doi.org/10.1007/s10528-017-9832-7

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