title: Characterization of retinoic acid-inducible gene-I (RIG-I) expression corresponding to viral infection and UVB in human keratinocytes.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Dermatology, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
authors.forename: Kazuyuki
authors.initials: K
authors.lastname: Kimura
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Matsuzaki
authors.forename: Yohei
authors.initials: Y
authors.lastname: Nishikawa
authors.forename: Hideo
authors.initials: H
authors.lastname: Kitamura
authors.forename: Eijiro
authors.initials: E
authors.lastname: Akasaka
authors.forename: Daiki
authors.initials: D
authors.lastname: Rokunohe
authors.forename: Hajime
authors.initials: H
authors.lastname: Nakano
authors.forename: Tadaatsu
authors.initials: T
authors.lastname: Imaizumi
authors.forename: Kei
authors.initials: K
authors.lastname: Satoh
authors.forename: Daisuke
authors.initials: D
authors.lastname: Sawamura
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology; D002461:Cell Line, Transformed; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000235:genetics* / Q000378:metabolism; D015870:Gene Expression / Q000502:physiology / Q000528:radiation effects; D006801:Humans; D050856:Interferon Regulatory Factor-1 / Q000235:genetics / Q000378:metabolism; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D011070:Poly I-C / Q000494:pharmacology; D011401:Promoter Regions, Genetic / Q000502:physiology; D011971:Receptors, Immunologic; D014466:Ultraviolet Rays; D014777:Virus Diseases / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D000998:Antiviral Agents; D050856:Interferon Regulatory Factor-1; D011971:Receptors, Immunologic; C452820:RIGI protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases; D011070:Poly I-C