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

Biochem Genet. 2018 Apr;56(1-2):93-102. doi: 10.1007/s10528-017-9832-7. Epub 2017 Nov 16.

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.

Keywords: GAS; IFN-γ; Keratinocyte; STING.

MeSH terms

  • Humans
  • Interferon-gamma / genetics
  • Interferon-gamma / metabolism*
  • Keratinocytes / cytology
  • Keratinocytes / metabolism*
  • Membrane Proteins / biosynthesis*
  • Membrane Proteins / genetics
  • Nucleotide Motifs*
  • Response Elements*
  • STAT1 Transcription Factor / genetics
  • STAT1 Transcription Factor / metabolism
  • Signal Transduction*
  • Up-Regulation*

Substances

  • IFNG protein, human
  • Membrane Proteins
  • STAT1 Transcription Factor
  • STAT1 protein, human
  • STING1 protein, human
  • Interferon-gamma