Characterization of retinoic acid-inducible gene-I (RIG-I) expression corresponding to viral infection and UVB in human keratinocytes

J Dermatol Sci. 2012 Apr;66(1):64-70. doi: 10.1016/j.jdermsci.2012.02.006. Epub 2012 Feb 21.


Background: Retinoic acid-inducible gene-I (RIG-I) is a cytoplasmic protein that recognizes viral double-stranded RNA to induce the type I interferon (IFN) response. In human keratinocytes, RIG-I is induced by IFN-γ and tumor necrosis factor-α stimulation, and is abundantly expressed in psoriatic keratinocytes of the spinous and basal layers.

Objective: This study investigated the effects of extraneous stimuli including viral infection and UVB exposure on RIG-I expression in human keratinocytes.

Methods: Human skin keratinocytes (HaCaT cells) were stimulated by polyinosinic-polycytidylic acid (poly(I:C)), which mimics viral infection, and UVB exposure. We assessed the expression of RIG-I and IFN-regulatory factor (IRF)-1 in HaCaT cells by RT-PCR and Western blot analysis. Moreover, we investigated the effect of IRF-1 binding site of RIG-I gene promoter on the regulation of RIG-I expression by luciferase promoter assay and electrophoretic mobility shift assay.

Results: Poly(I:C) induced RIG-I expression, while UVB inhibited basal RIG-I expression and the poly(I:C)-induced RIG-I overexpression in HaCaT cells. IRF-1, which binds to a regulatory element located on the RIG-I gene promoter, was required for both inductions of RIG-I expression. IRF-1 expression was enhanced three hours after the poly(I:C) stimulation, consistent with the RIG-I response to poly(I:C), and thereafter was suppressed. Moreover, UVB exposure promptly decreased IRF-1 expression, resulting in decreased IRF-1 protein binding to the RIG-I promoter, and consequently, decreased RIG-I expression.

Conclusion: Thus, suppression of RIG-I and IRF-1 expression caused by UVB exposure may partly explain the inhibition of skin-based immune responses, leading to viral infection and recrudescence.

MeSH terms

  • Antiviral Agents / pharmacology
  • Cell Line, Transformed
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases / genetics*
  • DEAD-box RNA Helicases / metabolism
  • Gene Expression / physiology
  • Gene Expression / radiation effects
  • Humans
  • Interferon Regulatory Factor-1 / genetics
  • Interferon Regulatory Factor-1 / metabolism
  • Keratinocytes / cytology
  • Keratinocytes / drug effects
  • Keratinocytes / physiology*
  • Poly I-C / pharmacology
  • Promoter Regions, Genetic / physiology
  • Receptors, Immunologic
  • Ultraviolet Rays
  • Virus Diseases / metabolism*
  • Virus Diseases / physiopathology


  • Antiviral Agents
  • Interferon Regulatory Factor-1
  • Receptors, Immunologic
  • DDX58 protein, human
  • DEAD Box Protein 58
  • DEAD-box RNA Helicases
  • Poly I-C