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

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.