title: Tumour necrosis factor-α plays a significant role in the Aldara-induced skin inflammation in mice.
abstract: BACKGROUND
  Recently, the Aldara-induced psoriasis-like skin inflammation model in mice has attracted increased attention, due to its dependence on the same immunological pathways and cell types as in human psoriasis.
  
  
  OBJECTIVE
  To study the impact of constitutive deficiency of tumour necrosis factor (TNF)-α and its upstream regulator mitogen-activated protein kinase-activated protein kinase 2 (MAPKAPK-2, herein MK2) in the Aldara-induced psoriasis-like skin inflammation model.
  
  
  METHODS
  TNF-α knockout (KO), MK2 KO and wild-type (WT) mice divided into separate groups received either 45-mg Aldara cream or control cream for 5 consecutive days. The skin inflammation was evaluated clinically, histologically, and by quantitative reverse transcription-polymerase chain reaction.
  
  
  RESULTS
  We found that TNF-α KO mice developed significantly less skin inflammation compared with WT mice, as evaluated clinically and histologically. At the molecular level, we demonstrated that the Aldara-induced mRNA expression of the psoriasis-related inflammatory markers interleukin (IL)-17C, IL-23p19, IL-12p40, IL-17A, IL-22 and S100A8 was significantly decreased in TNF-α KO mice compared with WT mice. No significant difference in the mRNA expression of these inflammatory markers between MK2 KO mice and WT mice was found, although Aldara-treated MK2 KO mice showed a tendency towards a lower mRNA expression of IL-17A and IL-22 compared with WT mice.
  
  
  CONCLUSIONS
  We were able to demonstrate significantly lower levels of inflammation in TNF-α KO mice compared with WT mice, supporting the use of this model in future studies characterizing the role of TNF-α in psoriasis.
authors.affiliation: Department of Dermatology, Aarhus University Hospital, P. P. Oerumsgade 11, Building 15B, DK-8000, Aarhus C, Denmark.
authors.forename: H
authors.initials: H
authors.lastname: Vinter
authors.affiliation: Department of Dermatology, Aarhus University Hospital, P. P. Oerumsgade 11, Building 15B, DK-8000, Aarhus C, Denmark.
authors.forename: K
authors.initials: K
authors.lastname: Kragballe
authors.affiliation: Department of Pathology, Aarhus University Hospital, Tage Hansens Gade 2, DK-8000, Aarhus C, Denmark.
authors.forename: T
authors.initials: T
authors.lastname: Steiniche
authors.affiliation: Institute of Biochemistry, Hannover Medical University, 30625, Hannover, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Gaestel
authors.affiliation: Department of Dermatology, Aarhus University Hospital, P. P. Oerumsgade 11, Building 15B, DK-8000, Aarhus C, Denmark.
authors.forename: L
authors.initials: L
authors.lastname: Iversen
authors.affiliation: Department of Dermatology, Aarhus University Hospital, P. P. Oerumsgade 11, Building 15B, DK-8000, Aarhus C, Denmark.
authors.forename: C
authors.initials: C
authors.lastname: Johansen
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000633:toxicity*; D000279:Administration, Cutaneous; D000634:Aminoquinolines / Q000008:administration & dosage / Q000633:toxicity*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D040501:Calgranulin A / Q000378:metabolism; D003875:Drug Eruptions / Q000209:etiology; D000077271:Imiquimod; D007378:Interleukins / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009824:Ointments / Q000008:administration & dosage / Q000633:toxicity; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D011565:Psoriasis / Q000139:chemically induced*; D012333:RNA, Messenger / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000502:physiology*; D000099190:MAP-Kinase-Activated Kinase 2
chemical_list: D000276:Adjuvants, Immunologic; D000634:Aminoquinolines; D015415:Biomarkers; D040501:Calgranulin A; D000077271:Imiquimod; D007378:Interleukins; D047908:Intracellular Signaling Peptides and Proteins; D009824:Ointments; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D000099190:MAP-Kinase-Activated Kinase 2; C086145:S100a8 protein, mouse