title: Changes in mRNA expression precede changes in microRNA expression in lesional psoriatic skin during treatment with adalimumab.
abstract: BACKGROUND
  Tumour necrosis factor (TNF)-α inhibition is an effective treatment for moderate to severe plaque-type psoriasis. A change in the cytokine expression profile occurs in the skin after 4 days of treatment, preceding any clinical or histological improvements. MicroRNAs (miRNAs) are important post-transcriptional regulators of gene expression, but miRNA expression has never been studied in psoriatic skin during treatment.
  
  
  OBJECTIVE
  To investigate changes in miRNA expression in psoriatic skin during adalimumab treatment and to compare results with changes in miRNA expression in a mouse model of Aldara-induced psoriasis-like skin inflammation.
  
  
  METHODS
  Punch biopsies were obtained from nonlesional and lesional psoriatic skin during adalimumab treatment. In the mouse model of Aldara-induced skin inflammation, biopsies were obtained from TNF-α knockout (KO), IL-17A KO and wild-type mice. miRNA expression levels were analysed with microarray, reverse transcriptase quantitative polymerase chain reaction and in situ hybridization.
  
  
  RESULTS
  In psoriatic skin, no changes in miRNA expression were seen 4 days after treatment initiation. After 14 days of treatment, the expression of several miRNAs was normalized towards the level seen in nonlesional skin before treatment. miR-23b expression increased after 14 days of treatment and remained high for 84 days, despite unaltered levels at baseline. In the mouse model of Aldara-induced skin inflammation, the level of miR-146a increased, whereas no regulation was seen for miR-203, miR-214-3p, miR-125a, miR-23b or let-7d-5p.
  
  
  CONCLUSIONS
  This study demonstrates that the changes seen in the cytokine expression levels after 4 days of treatment with adalimumab are not facilitated by early changes in miRNA expression.
authors: Department of Dermatology, Aarhus University Hospital, Aarhus, Denmark.
authors: L
authors: L
authors: Raaby
authors: Department of Dermatology, Aarhus University Hospital, Aarhus, Denmark.
authors: A
authors: A
authors: Langkilde
authors: Department of Dermatology, Aarhus University Hospital, Aarhus, Denmark.
authors: R B
authors: RB
authors: Kjellerup
authors: Department of Dermatology, Aarhus University Hospital, Aarhus, Denmark.
authors: H
authors: H
authors: Vinter
authors: Department of Dermatology, Aarhus University Hospital, Aarhus, Denmark.
authors: S H
authors: SH
authors: Khatib
authors: Department of Dermatology, Aarhus University Hospital, Aarhus, Denmark.
authors: K F
authors: KF
authors: Hjuler
authors: Department of Dermatology, Aarhus University Hospital, Aarhus, Denmark.
authors: C
authors: C
authors: Johansen
authors: Department of Dermatology, Aarhus University Hospital, Aarhus, Denmark.
authors: L
authors: L
authors: Iversen
mesh_terms: D000068879:Adalimumab / Q000494:pharmacology*; D000328:Adult; D000368:Aged; D000634:Aminoquinolines / Q000633:toxicity; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D016022:Case-Control Studies; D015536:Down-Regulation; D005260:Female; D006801:Humans; D000077271:Imiquimod; D016209:Interleukin-8 / Q000378:metabolism; D007509:Irritants / Q000633:toxicity; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D035683:MicroRNAs / Q000187:drug effects / Q000378:metabolism*; D008875:Middle Aged; D011565:Psoriasis / Q000188:drug therapy*; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism*
chemical_list: D000634:Aminoquinolines; D000893:Anti-Inflammatory Agents; D016209:Interleukin-8; D007509:Irritants; D035683:MicroRNAs; D012333:RNA, Messenger; D000068879:Adalimumab; D000077271:Imiquimod