title: Narrowband ultraviolet B inhibits innate cytosolic double-stranded RNA receptors in psoriatic skin and keratinocytes.
abstract: BACKGROUND
  The mode of action of narrowband ultraviolet B (NB-UVB) therapy in clearing psoriasis is incompletely understood, and in vivo studies at the molecular level in patients undergoing NB-UVB therapy are limited. We previously demonstrated increased expression and activity of double-stranded RNA (dsRNA) receptors in psoriasis lesions, and suggested that this enhanced innate signalling contributed to the maintenance of psoriatic inflammation.
  
  
  OBJECTIVE
  We investigated whether NB-UVB affects dsRNA receptor expression and function in vivo as well as in vitro.
  
  
  METHODS
  Skin samples of patients with psoriasis undergoing NB-UVB treatment were analysed for epidermal messenger RNA (mRNA) expression of the various dsRNA receptors by microarray and quantitative reverse transcription-polymerase chain reaction. Primary human keratinocytes were irradiated with NB-UVB and stimulated with interferon (IFN)-α or IFN-γ, critical cytokines in psoriasis. The dsRNA analogue polyriboinosinic-polyribocytidylic acid was used to assess the functional responsiveness of the cells to dsRNA.
  
  
  RESULTS
  NB-UVB therapy of patients with psoriasis resulted in a significantly reduced mRNA expression of the activating dsRNA receptors MDA5 (IFIH1) and RIG-I (DDX58). On the other hand, expression of LGP2 (DHX58), toll-like receptor 3 (TLR3) and PKR (EIF2AK2) was not affected. In vitro, NB-UVB irradiation completely blocked the upregulation of four of the dsRNA receptors in primary human keratinocytes stimulated with IFN-α or IFN-γ, resulting in an attenuated inflammatory response to dsRNA.
  
  
  CONCLUSIONS
  Our results show that NB-UVB irradiation inhibits the local innate inflammatory response to dsRNA, and suggest a novel mechanism of action of NB-UVB phototherapy in psoriasis.
authors.affiliation: Departments of Dermatology Immunology Genetics, Erasmus MC, University Medical Center, PO Box 2040, 3000 CA Rotterdam, the Netherlands.
authors.forename: E
authors.initials: E
authors.lastname: Rácz
authors.forename: E P
authors.initials: EP
authors.lastname: Prens
authors.forename: M
authors.initials: M
authors.lastname: Kant
authors.forename: E
authors.initials: E
authors.lastname: Florencia
authors.forename: N G
authors.initials: NG
authors.lastname: Jaspers
authors.forename: J D
authors.initials: JD
authors.lastname: Laman
authors.forename: D
authors.initials: D
authors.lastname: de Ridder
authors.forename: L
authors.initials: L
authors.lastname: van der Fits
mesh_terms: D000328:Adult; D000368:Aged; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000378:metabolism; D005260:Female; D006801:Humans; D000072640:Interferon-Induced Helicase, IFIH1; D007372:Interferons / Q000494:pharmacology; D015603:Keratinocytes / Q000378:metabolism / Q000528:radiation effects; D008297:Male; D046228:Microarray Analysis; D008875:Middle Aged; D011565:Psoriasis / Q000378:metabolism / Q000532:radiotherapy; D020365:RNA Helicases / Q000378:metabolism; D012330:RNA, Double-Stranded / Q000378:metabolism / Q000528:radiation effects*; D012333:RNA, Messenger / Q000378:metabolism / Q000528:radiation effects; D011971:Receptors, Immunologic; D051192:Receptors, Pattern Recognition / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000378:metabolism / Q000528:radiation effects; D051196:Toll-Like Receptor 3 / Q000378:metabolism; D014467:Ultraviolet Therapy / Q000379:methods
chemical_list: D012330:RNA, Double-Stranded; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D051192:Receptors, Pattern Recognition; D051196:Toll-Like Receptor 3; D007372:Interferons; C520569:DHX58 protein, human; C452820:RIGI protein, human; C452815:IFIH1 protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases; D000072640:Interferon-Induced Helicase, IFIH1; D020365:RNA Helicases