title: Resveratrol ameliorates imiquimod-induced psoriasis-like skin inflammation in mice.
abstract: BACKGROUND
  The polyphenol resveratrol has anti-inflammatory effects in various cells, tissues, animals and human settings of low-grade inflammation. Psoriasis is a disease of both localized and systemic low-grade inflammation. The Sirtuin1 enzyme thought to mediate the effects of resveratrol is present in skin and resveratrol is known to down regulate NF-κB; an important contributor in the development of psoriasis. Consequently we investigated whether resveratrol has an effect on an Imiquimod induced psoriasis-like skin inflammation in mice and sought to identify candidate genes, pathways and interleukins mediating the effects.
  
  
  METHODS
  The study consisted of three treatment groups: A control group, an Imiquimod group and an Imiquimod+resveratrol group. Psoriasis severity was assessed using elements of the Psoriasis Area Severity Index, skin thickness measurements, and histological examination. We performed an RNA microarray from lesional skin and afterwards Ingenuity pathway analysis to identify affected signalling pathways. Our microarray was compared to a previously deposited microarray to determine if gene changes were psoriasis-like, and to a human microarray to determine if findings could be relevant in a human setting.
  
  
  RESULTS
  Imiquimod treatment induced a psoriasis-like skin inflammation. Resveratrol significantly diminished the severity of the psoriasis-like skin inflammation. The RNA microarray revealed a psoriasis-like gene expression-profile in the Imiquimod treated group, and highlighted several resveratrol dependent changes in relevant genes, such as increased expression of genes associated with retinoic acid stimulation and reduced expression of genes involved in IL-17 dependent pathways. Quantitative PCR confirmed a resveratrol dependent decrease in mRNA levels of IL-17A and IL-19; both central in developing psoriasis.
  
  
  CONCLUSIONS
  Resveratrol ameliorates psoriasis, and changes expression of retinoic acid stimulated genes, IL-17 signalling pathways, IL-17A and IL-19 mRNA levels in a beneficial manner, which suggests resveratrol, might have a role in the treatment of psoriasis and should be explored further in a human setting.
authors.affiliation: Department of Endocrinology and Internal medicine, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
authors.forename: Thomas Nordstrøm
authors.initials: TN
authors.lastname: Kjær
authors.affiliation: Department of Clinical Medicine, Aarhus University, Aarhus, Denmark; Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Kasper
authors.initials: K
authors.lastname: Thorsen
authors.affiliation: Department of Clinical Medicine, Aarhus University, Aarhus, Denmark; Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Niels
authors.initials: N
authors.lastname: Jessen
authors.affiliation: Department of Clinical Medicine, Aarhus University, Aarhus, Denmark; Department of Dermatology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Karin
authors.initials: K
authors.lastname: Stenderup
authors.affiliation: Department of Endocrinology and Internal medicine, Aarhus University Hospital, Aarhus, Denmark; Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
authors.forename: Steen Bønløkke
authors.initials: SB
authors.lastname: Pedersen
mesh_terms: D000634:Aminoquinolines; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000494:pharmacology; D004195:Disease Models, Animal; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D000077271:Imiquimod; D007378:Interleukins / Q000235:genetics; D008297:Male; D051379:Mice; D011565:Psoriasis / Q000139:chemically induced* / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D000077185:Resveratrol; D015398:Signal Transduction / Q000187:drug effects*; D013267:Stilbenes / Q000008:administration & dosage* / Q000494:pharmacology
chemical_list: D000634:Aminoquinolines; D000894:Anti-Inflammatory Agents, Non-Steroidal; D007378:Interleukins; D013267:Stilbenes; D000077271:Imiquimod; D000077185:Resveratrol